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Cd2+ cation doped CsPbCl3 single crystals were synthesized, and their luminescent properties were investigated under excitation with synchrotron radiation quanta with energy greater than Eg and at a sample temperature of 12 K. Pure single crystals exhibit a narrow band of exciton emission at 416.7 nm. Doping the single crystals leads to a high-energy shift of the excitonic luminescence, the appearance of new luminescent bands, the broadening of the luminescent bands, an increase in the decay time constants, and a significant enhancement of the luminescence intensity. The observed changes in luminescent parameters upon doping are discussed in terms of the crystal structure ordering, a decrease in the number of defects responsible for capturing charge carriers at the stage of electronic excitation thermalization, and a decrease in defects that quench excitonic luminescence. Doped single crystals with decay times of the order of 0.4 ns and intensities that significantly exceed the intensity of pure single crystals can be promising scintillation materials for positron emission tomography in the time-of-flight mode. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) stand as pivotal diagnostic tools for brain disorders, offering the potential for mutually enriching disease diagnostic perspectives. However, the costs associated with PET scans and the inherent radioactivity have limited the widespread application of PET. Furthermore, it is noteworthy to highlight the promising potential of high‐field and ultra‐high‐field neuroimaging in cognitive neuroscience research and clinical practice. With the enhancement of MRI resolution, a related question arises: can high‐resolution MRI improve the quality of PET images?This study aims to enhance the quality of synthesized PET images by leveraging the superior resolution capabilities provided by high‐field and ultra‐high‐field MRI.From a statistical perspective, the joint probability distribution is considered the most direct and fundamental approach for representing the correlation between PET and MRI. In this study, we proposed a novel model, the joint diffusion attention model, namely, the joint diffusion attention model (JDAM), which primarily focuses on learning information about the joint probability distribution. JDAM consists of two primary processes: the diffusion process and the sampling process. During the diffusion process, PET gradually transforms into a Gaussian noise distribution by adding Gaussian noise, while MRI remains fixed. The central objective of the diffusion process is to learn the gradient of the logarithm of the joint probability distribution between MRI and noise PET. The sampling process operates as a predictor‐corrector. The predictor initiates a reverse diffusion process, and the corrector applies Langevin dynamics.Experimental results from the publicly available Alzheimer's Disease Neuroimaging Initiative dataset highlight the effectiveness of the proposed model compared to state‐of‐the‐art (SOTA) models such as Pix2pix and CycleGAN. Significantly, synthetic PET images guided by ultra‐high‐field MRI exhibit marked improvements in signal‐to‐noise characteristics when contrasted with those generated from high‐field MRI data. These results have been endorsed by medical experts, who consider the PET images synthesized through JDAM to possess scientific merit. This endorsement is based on their symmetrical features and precise representation of regions displaying hypometabolism, a hallmark of Alzheimer's disease.This study establishes the feasibility of generating PET images from MRI. Synthesis of PET by JDAM significantly enhances image quality compared to SOTA models. [ABSTRACT FROM AUTHOR]

Background: The axillary lymph-node metastatic burden is closely associated with treatment decisions and prognosis in breast cancer patients. This study aimed to explore the value of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT)–based radiomics in combination with ultrasound and clinical pathological features for predicting axillary lymph-node metastatic burden in breast cancer. Methods: A retrospective analysis was conducted and involved 124 patients with pathologically confirmed early-stage breast cancer who had undergone 18F-FDG PET/CT examination. The ultrasound, PET/CT, and clinical pathological features of all patients were analysed, and radiomic features from PET images were extracted to establish a multi-parameter predictive model. Results: The ultrasound lymph-node positivity rate and PET lymph-node positivity rate in the high nodal burden group were significantly higher than those in the low nodal burden group (χ2 = 19.867, p < 0.001; χ2 = 33.025, p < 0.001). There was a statistically significant difference in the PET-based radiomics score (RS) for predicting axillary lymph-node burden between the high and low lymph-node burden groups. (-1.04 ± 0.41 vs. -1.47 ± 0.41, t = -4.775, p < 0.001). The ultrasound lymph-node positivity (US_LNM) (odds ratio [OR] = 3.264, 95% confidence interval [CI] = 1.022–10.423), PET lymph-node positivity (PET_LNM) (OR = 14.242, 95% CI = 2.960–68.524), and RS (OR = 5.244, 95% CI = 3.16–20.896) are all independent factors associated with high lymph-node burden (p < 0.05). The area under the curve (AUC) of the multi-parameter (MultiP) model was 0.895, which was superior to those of US_LNM, PET_LNM, and RS models (AUC = 0.703, 0.814, 0.773, respectively), with statistically significant differences (Z = 2.888, 3.208, 3.804, respectively; p = 0.004, 0.002, < 0.001, respectively). Decision curve analysis indicated that the MultiP model provided a higher net benefit for all patients. Conclusion: A MultiP model based on PET-based radiomics was able to effectively predict axillary lymph-node metastatic burden in breast cancer. Trial registration: This study was registered with ClinicalTrials.gov (registration number: NCT05826197) on May 7, 2023. [ABSTRACT FROM AUTHOR]

Background: [18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) is recommended during diagnostic work-up for ovarian cancer; however, [18F]FDG PET has several inherent limitations. The novel oncologic PET-tracer fibroblast activation protein inhibitor (FAPI) has demonstrated promising results in multiple cancer types, including ovarian cancer, and could overcome the limitations of [18F]FDG PET; however, high-quality clinical studies are lacking. The primary objective of the present study is to compare the diagnostic accuracy of [68Ga]Ga-FAPI-46 PET/CT and [18F]FDG PET/CT in ovarian cancer patients and to investigate how this potential difference impacts staging and patient management. Methods and design: Fifty consecutive ovarian cancer patients will be recruited from Aalborg University Hospital, Denmark. This study will be a single-center, prospective, exploratory clinical trial that adheres to the standards for reporting diagnostic accuracy studies (STARD). This study will be conducted under continuous Good Clinical Practice monitoring. The eligibility criteria for patients are as follows: (1) biopsy verified newly diagnosed ovarian cancer or a high risk of ovarian cancer and referred for primary staging with [18F]FDG PET/CT; and (2) resectable disease, i.e., candidate for primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery. All recruited study subjects will undergo [68Ga]Ga-FAPI-46 PET/CT at primary staging, before primary debulking surgery or neoadjuvant chemotherapy (Group A + B), in addition to conventional imaging (including [18F]FDG PET/CT). Study subjects in Group B will undergo an additional [68Ga]Ga-FAPI-46 PET/CT following neoadjuvant chemotherapy prior to interval debulking surgery. The results of the study-related [68Ga]Ga-FAPI-46 PET/CTs will be blinded, and treatment allocation will be based on common clinical practice in accordance with current guidelines. The histopathology of surgical specimens will serve as a reference standard. A recruitment period of 2 years is estimated; the trial is currently recruiting. Discussion: To our knowledge, this trial represents the largest, most extensive, and most meticulous prospective FAPI PET study conducted in patients with ovarian cancer thus far. This study aims to obtain a reliable estimation of the diagnostic accuracy of [68Ga]Ga-FAPI-46 PET/CT, shed light on the clinical importance of [68Ga]Ga-FAPI-46 PET/CT, and examine the potential applicability of [68Ga]Ga-FAPI-46 PET/CT for evaluating chemotherapy response. Trial registration: clinicaltrials.gov: NCT05903807, 2nd June 2023; and euclinicaltrials.eu EU CT Number: 2023-505938-98-00, authorized 11th September 2023. [ABSTRACT FROM AUTHOR]

It has been a big challenge to distinguish synchronous multiple primary lung cancer (sMPLC) from primary lung cancer with intrapulmonary metastases (IPM). We aimed to assess the clinical application of dynamic 18F-FDG PET/CT in patients with multiple lung cancer nodules. We enrolled patients with multiple pulmonary nodules who had undergone dynamic 18F-FDG PET/CT and divided them into sMPLC and IPM groups based on comprehensive features. The SUVmax, fitted K i value based on dynamic scanning, and corresponding maximum diameter ( D max ) from the two largest tumors were determined in each patient. We determined the absolute between-tumor difference of SU V max / D max and K i / D max (Δ SU V max / D max ; Δ K i / D max ) and assessed the between-group differences. Further, the diagnostic accuracy was evaluated by ROC analysis and the correlation between Δ SU V max / D max and Δ K i / D max from all groups was determined. There was no significant difference for Δ SU V max / D max between the IPM and sMPLC groups, while the IPM group had a significantly higher Δ K i / D max than the sMPLC group. The AUC of Δ K i / D max for differentiating sMPLC from IPM was 0.80 (cut-off value of K i = 0.0059 , sensitivity 79%, specificity 75%, p < 0.001). There was a good correlation (Pearson r = 0.91 , 95% CI: 0.79-0.96, p < 0.0001) between Δ SU V max / D max and Δ K i / D max in the IPM group but not in the sMPLC group (Pearson r = 0.45 , p > 0.05). Dynamic 18F-FDG PET/CT could be a useful tool for distinguishing sMPLC from IPM. K i calculation based on Patlak graphic analysis could be more sensitive than SUVmax in discriminating IPM from sMPLC in patients with multiple lung cancer nodules. [ABSTRACT FROM AUTHOR]

Background: Signal transducer and activator of transcription 3 (STAT3) is a protein that regulates cell proliferation and differentiation, and it is attracting attention as a new index for evaluating cancer pathophysiology, as its activation has been highly correlated with the development and growth of tumors. With the development of STAT3 inhibitors, the demand for imaging probes will intensify. Noninvasive STAT3 imaging can help determine the cancer status and predict the efficacy of STAT3 inhibitors. In this study, we aimed to develop an imaging probe targeting STAT3 and synthesized [18F]FBNAF, which was derived from a STAT3-selective inhibitor as the lead compound, followed by in vitro and in vivo evaluations of [18F]FBNAF in positron emission tomography for STAT3. Results: The results revealed that FBNAF concentration-dependently inhibited STAT3 phosphorylation, similar to the lead compound, thereby supporting radiosynthesis. [18F]FBNAF was easily synthesized from the pinacol boronate ester precursor with suitable radiochemical conversion (46%), radiochemical yield (6.0%), and radiochemical purity (> 97%). [18F]FBNAF exhibited high stability in vitro and in vivo, and radioactivity accumulated in tumor tissues expressing STAT3 with an increasing tumor/blood ratio over time, peaking at 2.6 ± 0.8 at 120 min after injection in tumor-bearing mice. Tumor radioactivity was significantly reduced by the coinjection of a STAT3-selective inhibitor. Furthermore, the localization of radioactivity was almost consistent with STAT3 expression based on ex vivo autoradiography and immunohistochemistry using adjacent tumor sections. Conclusions: Thus, [18F]FBNAF could be the first promising STAT3-targeting probe for PET imaging. A STAT3 imaging probe provides meaningful information on STAT3-associated cancer conditions and in tumor microenvironment. [ABSTRACT FROM AUTHOR]

Background: Histone deacetylase 6 (HDAC6) is an emerging target for the treatment and diagnosis of proteinopathies. [18F]FSW-100 was recently developed as a promising brain-penetrating radioligand for HDAC6 PET imaging and the process validation of [18F]FSW-100 radiosynthesis for clinical use is complete, but no detailed synthetic strategy nor process optimisation has been reported. Here, we describe the optimisation of several processes in [18F]FSW-100 radiosynthesis, including the 18F-fluorination reaction, semipurification of the 18F-intermediate, and purification of the product by high-performance liquid chromatography (HPLC), to achieve a radiochemical yield (RCY) adequate for clinical applications of the radioligand. Our findings will aid optimisation of radiosynthesis processes in general. Results: In the 18F-fluorination reaction, the amount of copper reagent was reduced without reducing the nonisolated RCY of the intermediate (50%), thus reducing the risk of copper contamination in the product injection solution. Optimising the solid-phase extraction (SPE) conditions for semipurification of the intermediate improved its recovery efficiency. The addition of anti-radiolysis reagents to the mobile phase for the HPLC purification of [18F]FSW-100 increased its activity yield in radiosynthesis using a high [18F]fluoride radioactivity of approximately 50 GBq. The SPE-based formulation method and additives for the injection solution were optimised, and the resulting [18F]FSW-100 injection solution was stable for over 2 h with a radiochemical purity of greater than 95%. Conclusions: Of all the reconsidered processes, we found that optimisation of the SPE-based semipurification of the intermediate and of the mobile phase for HPLC purification in particular improved the RCY of [18F]FSW-100, doubling it compared to that of the original protocol. The radioactivity of [18F]FSW-100 synthesized using the optimized protocol was sufficient for multiple doses for a clinical study. [ABSTRACT FROM AUTHOR]

Total coronary atherosclerotic plaque activity across the entire coronary arterial tree is associated with patient-level clinical outcomes. We aimed to investigate whether vessel-level coronary atherosclerotic plaque activity is associated with vessel-level myocardial infarction. In this secondary analysis of an international multicenter study of patients with recent myocardial infarction and multivessel coronary artery disease, we assessed vessel-level coronary atherosclerotic plaque activity using coronary 18F-sodium fluoride positron emission tomography to identify vessel-level myocardial infarction. Increased 18F-sodium fluoride uptake was found in 679 of 2,094 coronary arteries and 414 of 691 patients. Myocardial infarction occurred in 24 (4%) vessels with increased coronary atherosclerotic plaque activity and in 25 (2%) vessels without increased coronary atherosclerotic plaque activity (HR: 2.08; 95% CI: 1.16-3.72; P = 0.013). This association was not demonstrable in those treated with coronary revascularization (HR: 1.02; 95% CI: 0.47-2.25) but was notable in untreated vessels (HR: 3.86; 95% CI: 1.63-9.10; P interaction = 0.024). Increased coronary atherosclerotic plaque activity in multiple coronary arteries was associated with heightened patient-level risk of cardiac death or myocardial infarction (HR: 2.43; 95% CI: 1.37-4.30; P = 0.002) as well as first (HR: 2.19; 95% CI: 1.18-4.06; P = 0.013) and total (HR: 2.50; 95% CI: 1.42-4.39; P = 0.002) myocardial infarctions. In patients with recent myocardial infarction and multivessel coronary artery disease, coronary atherosclerotic plaque activity prognosticates individual coronary arteries and patients at risk for myocardial infarction. [Display omitted] [ABSTRACT FROM AUTHOR]

Objectives: To compare prostate-specific membrane antigen (PSMA) PET with multiparametric MRI (mpMRI) in the diagnosis of pretreatment prostate cancer (PCa). Methods: Pubmed, Embase, Medline, Web of Science, and Cochrane Library were searched for eligible studies published before June 22, 2022. We assessed risk of bias and applicability by using QUADAS-2 tool. Data synthesis was performed with Stata 17.0 software, using the "midas" and "meqrlogit" packages. Results: We included 29 articles focusing on primary cancer detection, 18 articles about primary staging, and two articles containing them both. For PSMA PET versus mpMRI in primary PCa detection, sensitivities and specificities in the per-patient analysis were 0.90 and 0.84 (p<0.0001), and 0.66 and 0.60 (p <0.0001), and in the per-lesion analysis they were 0.79 and 0.78 (p <0.0001), and 0.84 and 0.82 (p <0.0001). For the per-patient analysis of PSMA PET versus mpMRI in primary staging, sensitivities and specificities in extracapsular extension detection were 0.59 and 0.66 (p =0.005), and 0.79 and 0.76 (p =0.0074), and in seminal vesicle infiltration (SVI) detection they were 0.51 and 0.60 (p =0.0008), and 0.93 and 0.96 (p =0.0092). For PSMA PET versus mpMRI in lymph node metastasis (LNM) detection, sensitivities and specificities in the per-patient analysis were 0.68 and 0.46 (p <0.0001), and 0.91 and 0.90 (p =0.81), and in the per-lesion analysis they were 0.67 and 0.36 (p <0.0001), and 0.99 and 0.99 (p =0.18). Conclusion: PSMA PET has higher diagnostic value than mpMRI in the detection of primary PCa. Regarding the primary staging, mpMRI has potential advantages in SVI detection, while PSMA PET has relative advantages in LNM detection. Clinical relevance statement: The integration of prostate-specific membrane antigen (PSMA) PET into the diagnostic pathway may be helpful for improving the accuracy of prostate cancer detection. However, further studies are needed to address the cost implications and evaluate its utility in specific patient populations or clinical scenarios. Moreover, we recommend the combination of PSMA PET and mpMRI for cancer staging. Key Points: • Prostate-specific membrane antigen PET has higher sensitivity and specificity for primary tumor detection in prostate cancer compared to multiparametric MRI. • Prostate-specific membrane antigen PET also has significantly better sensitivity and specificity for lymph node metastases of prostate cancer compared to multiparametric MRI. • Multiparametric MRI has better accuracy for extracapsular extension and seminal vesicle infiltration compared to ate-specific membrane antigen PET. [ABSTRACT FROM AUTHOR]

Sonodynamic therapy (SDT) has emerged as a useful approach for tumor treatment. However, its widespread application is impeded by poor pharmacokinetics of existing sonosensitizers. Here we developed a metal-organic nanoplatform, wherein a small-molecule sonosensitizer (hematoporphyrin monomethyl ether, HMME) was ingeniously coordinated with zirconium, resulting in a multifunctional nanosonosensitizer termed Zr-HMME. Through post-synthetic modifications involving PEGylation and tumor-targeting peptide (F3) linkage, a nanoplatform capable of homing on melanoma was produced, which could elicit robust immune responses to suppress tumor lung metastasis in the host organism. Importantly, after seamless incorporation of positron-emitting 89Zr into this nanosonosensitizer, positron emission tomography (PET) could be used to monitor its in vivo pharmacokinetics. PET imaging studies revealed that this nanoplatform exhibited potent tumor accumulation and strong in vivo stability. Using intrinsic fluorescence from HMME, a dual-modal diagnostic capability (fluorescence and PET) was confirmed for this nanosonosensitizer. In addition, the mechanisms of how this nanoplatform interacted with immune system were also investigated. The collective data proved that the coordination structure between small-molecule drug cargos and metals may enhance the functions of each other while mitigating their weaknesses. This straightforward approach can expand the potential applications of suitable drug molecules. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Biology‐guided radiotherapy (BgRT) is a novel radiotherapy delivery technique that utilizes the tumor itself to guide dynamic delivery of treatment dose to the tumor. The RefleXion X1 system is the first radiotherapy system developed to deliver SCINTIX® BgRT. The X1 is characterized by its split arc design, employing two 90‐degree positron emission tomography (PET) arcs to guide therapeutic radiation beams in real time, currently cleared by FDA to treat bone and lung tumors. Purpose: This study aims to comprehensively evaluate the capabilities of the SCINTIX radiotherapy delivery system by evaluating its sensitivity to changes in PET contrast, its adaptability in the context of patient motion, and its performance across a spectrum of prescription doses. Methods: A series of experimental scenarios, both static and dynamic, were designed to assess the SCINTIX BgRT system's performance, including an end‐to‐end test. These experiments involved a range of factors, including changes in PET contrast, motion, and prescription doses. Measurements were performed using a custom‐made ArcCHECK insert which included a 2.2 cm spherical target and a c‐shape structure that can be filled with a PET tracer with varying concentrations. Sinusoidal and cosine4 motion patterns, simulating patient breathing, was used to test the SCINTIX system's ability to deliver BgRT during motion‐induced challenges. Each experiment was evaluated against specific metrics, including Activity Concentration (AC), Normalized Target Signal (NTS), and Biology Tracking Zone (BTZ) bounded dose‐volume histogram (bDVH) pass rates. The accuracy of the delivered BgRT doses on ArcCHECK and EBT‐XD film were evaluated using gamma 3%/2 mm and 3%/3 mm analysis. Results: In static scenarios, the X1 system consistently demonstrated precision and robustness in SCINTIX dose delivery. The end‐to‐end delivery to the spherical target yielded good results, with AC and NTS values surpassing the critical thresholds of 5 kBq/mL and 2, respectively. Furthermore, bDVH analysis consistently confirmed 100% pass rates. These results were reaffirmed in scenarios involving changes in PET contrast, emphasizing the system's ability to adapt to varying PET avidities. Gamma analysis with 3%/2 mm (10% dose threshold) criteria consistently achieved pass rates > 91.5% for the static tests. In dynamic SCINTIX delivery scenarios, the X1 system exhibited adaptability under conditions of motion. Sinusoidal and cosine4 motion patterns resulted in 3%/3 mm gamma pass rates > 87%. Moreover, the comparison with gated stereotactic body radiotherapy (SBRT) delivery on a conventional c‐arm Linac resulted in 93.9% gamma pass rates and used as comparison to evaluate the interplay effect. The 1 cm step shift tests showed low overall gamma pass rates of 60.3% in ArcCHECK measurements, while the doses in the PTV agreed with the plan with 99.9% for 3%/3 mm measured with film. Conclusions: The comprehensive evaluation of the X1 radiotherapy delivery system for SCINTIX BgRT demonstrated good agreement for the static tests. The system consistently achieved critical metrics and delivered the BgRT doses per plan. The motion tests demonstrated its ability to co‐localize the dose where the PET signal is and deliver acceptable BgRT dose distributions. [ABSTRACT FROM AUTHOR]

Background: Preclinical low‐count positron emission tomography (LC‐PET) imaging offers numerous advantages such as facilitating imaging logistics, enabling longitudinal studies of long‐ and short‐lived isotopes as well as increasing scanner throughput. However, LC‐PET is characterized by reduced photon‐count levels resulting in low signal‐to‐noise ratio (SNR), segmentation difficulties, and quantification uncertainties. Purpose: We developed and evaluated a novel deep‐learning (DL) architecture—Attention based Residual‐Dilated Net (ARD‐Net)—to generate standard‐count PET (SC‐PET) images from LC‐PET images. The performance of the ARD‐Net framework was evaluated for numerous low count realizations using fidelity‐based qualitative metrics, task‐based segmentation, and quantitative metrics. Method: Patient Derived tumor Xenograft (PDX) with tumors implanted in the mammary fat‐pad were subjected to preclinical [18F]‐Fluorodeoxyglucose (FDG)‐PET/CT imaging. SC‐PET images were derived from a 10 min static FDG‐PET acquisition, 50 min post administration of FDG, and were resampled to generate four distinct LC‐PET realizations corresponding to 10%, 5%, 1.6%, and 0.8% of SC‐PET count‐level. ARD‐Net was trained and optimized using 48 preclinical FDG‐PET datasets, while 16 datasets were utilized to assess performance. Further, the performance of ARD‐Net was benchmarked against two leading DL‐based methods (Residual UNet, RU‐Net; and Dilated Network, D‐Net) and non‐DL methods (Non‐Local Means, NLM; and Block Matching 3D Filtering, BM3D). The performance of the framework was evaluated using traditional fidelity‐based image quality metrics such as Structural Similarity Index Metric (SSIM) and Normalized Root Mean Square Error (NRMSE), as well as human observer‐based tumor segmentation performance (Dice Score and volume bias) and quantitative analysis of Standardized Uptake Value (SUV) measurements. Additionally, radiomics‐derived features were utilized as a measure of quality assurance (QA) in comparison to true SC‐PET. Finally, a performance ensemble score (EPS) was developed by integrating fidelity‐based and task‐based metrics. Concordance Correlation Coefficient (CCC) was utilized to determine concordance between measures. The non‐parametric Friedman Test with Bonferroni correction was used to compare the performance of ARD‐Net against benchmarked methods with significance at adjusted p‐value ≤0.01. Results: ARD‐Net‐generated SC‐PET images exhibited significantly better (p ≤ 0.01 post Bonferroni correction) overall image fidelity scores in terms of SSIM and NRMSE at majority of photon‐count levels compared to benchmarked DL and non‐DL methods. In terms of task‐based quantitative accuracy evaluated by SUVMean and SUVPeak, ARD‐Net exhibited less than 5% median absolute bias for SUVMean compared to true SC‐PET and lower degree of variability compared to benchmarked DL and non‐DL based methods in generating SC‐PET. Additionally, ARD‐Net‐generated SC‐PET images displayed higher degree of concordance to SC‐PET images in terms of radiomics features compared to non‐DL and other DL approaches. Finally, the ensemble score suggested that ARD‐Net exhibited significantly superior performance compared to benchmarked algorithms (p ≤ 0.01 post Bonferroni correction). Conclusion: ARD‐Net provides a robust framework to generate SC‐PET from LC‐PET images. ARD‐Net generated SC‐PET images exhibited superior performance compared other DL and non‐DL approaches in terms of image‐fidelity based metrics, task‐based segmentation metrics, and minimal bias in terms of task‐based quantification performance for preclinical PET imaging. [ABSTRACT FROM AUTHOR]

Background: High‐resolution brain positron emission tomography (PET) scanner is emerging as a significant and transformative non‐invasive neuroimaging tool to advance neuroscience research as well as improve diagnosis and treatment in neurology and psychiatry. Time‐of‐flight (TOF) and depth‐of‐interaction (DOI) information provide markedly higher PET imaging performance by increasing image signal‐to‐noise ratio and mitigating spatial resolution degradation due to parallax error, respectively. PET detector modules that utilize light sharing can inherently carry DOI information from the multiple timestamps that are generated per gamma event. The difference between two timestamps that are triggered by scintillation photons traveling in opposite directions signifies the event's depth‐dependent optical photon TOF (oTOF). However, light leak at the crystal‐readout interface substantially degrades the resolution of this oTOF‐based depth encoding. Purpose: We demonstrate the feasibility of oTOF‐based depth encoding by mitigating light leak in single‐ended‐readout Prism‐PET detector modules using tapered crystals. Minimizing light leak also improved both energy‐based DOI and coincidence timing resolutions. Methods: The tapered Prism‐PET module consists of a 16 ×$\times$ 16 array of 1.5 ×$\times$ 1.5 ×$\times$ 20 mm3${\rm {mm}}^3$ lutetium yttrium oxyorthosillicate (LYSO) crystals, which are tapered down to 1.2 ×$\times$ 1.2 mm2${\rm {mm}}^2$ at the crystal‐readout interface. The LYSO array couples 4‐to‐1 to an 8 ×$\times$ 8 array of 3 ×$\times$ 3 mm2${\rm {mm}}^2$ silicon photomultiplier (SiPM) pixels on the tapered end and to a segmented prismatoid light guide array on the opposite end. Performance of tapered and non‐tapered Prism‐PET detectors was experimentally characterized and evaluated by measuring flood histogram, energy resolution, energy‐, and oTOF‐based DOI resolutions, and coincidence timing resolution. Sensitivities of scanners using different Prism‐PET detector designs were simulated using Geant4 application for tomographic emission (GATE). Results: For the tapered (non‐tapered) Prism‐PET module, the measured full width at half maximum (FWHM) energy, timing, energy‐based DOI, and oTOF‐based DOI resolutions were 8.88 (11.18)%, 243 (286) ps, 2.35 (3.18) mm, and 5.42 (13.87) mm, respectively. The scanner sensitivities using non‐tapered and tapered crystals, and 10 rings of detector modules, were simulated to be 30.9 and 29.5 kcps/MBq, respectively. Conclusions: The tapered Prism‐PET module with minimized light leak enabled the first experimental report of oTOF‐based depth encoding at the detector module level. It also enabled the utilization of thinner (i.e., 0.1 mm) inter‐crystal spacing with barium sulfate as the reflector while also improving energy‐based DOI and timing resolutions. [ABSTRACT FROM AUTHOR]

Purpose: Assessing renal perfusion in‐vivo is challenging and quantitative information regarding renal hemodynamics is hardly incorporated in medical decision‐making while abnormal renal hemodynamics might play a crucial role in the onset and progression of renal disease. Combining physiological stimuli with rubidium‐82 positron emission tomography/computed tomography (82Rb PET/CT) offers opportunities to test the kidney perfusion under various conditions. The aim of this study is: (1) to investigate the application of a one‐tissue compartment model for measuring renal hemodynamics with dynamic 82Rb PET/CT imaging, and (2) to evaluate whether dynamic PET/CT is sensitive to detect differences in renal hemodynamics in stress conditions compared to resting state. Methods: A one‐tissue compartment model for the kidney was applied to cardiac 82Rb PET/CT scans that were obtained for ischemia detection as part of clinical care. Retrospective data, collected from 17 patients undergoing dynamic myocardial 82Rb PET/CT imaging in rest, were used to evaluate various CT‐based volumes of interest (VOIs) of the kidney. Subsequently, retrospective data, collected from 10 patients (five impaired kidney functions and five controls) undergoing dynamic myocardial 82Rb PET/CT imaging, were used to evaluate image‐derived input functions (IDIFs), PET‐based VOIs of the kidney, extraction fractions, and whether dynamic 82Rb PET/CT can measure renal hemodynamics differences using the renal blood flow (RBF) values in rest and after exposure to adenosine pharmacological stress. Results: The delivery rate (K1) values showed no significant (p = 0.14) difference between the mean standard deviation (SD) K1 values using one CT‐based VOI and the use of two, three, and four CT‐based VOIs, respectively 2.01(0.32), 1.90(0.40), 1.93(0.39), and 1.94(0.40) mL/min/mL. The ratio between RBF in rest and RBF in pharmacological stress for the controls were overall significantly lower compared to the impaired kidney function group for both PET‐based delineation methods (region growing and iso‐contouring), with the smallest median interquartile range (IQR) of 0.40(0.28–0.66) and 0.96(0.62–1.15), respectively (p < 0.05). The K1 of the impaired kidney function group were close to 1.0 mL/min/mL. Conclusions: This study demonstrated that obtaining renal K1 and RBF values using 82Rb PET/CT was feasible using a one‐tissue compartment model. Applying iso‐contouring as the PET‐based VOI of the kidney and using AA as an IDIF is suggested for consideration in further studies. Dynamic 82Rb PET/CT imaging showed significant differences in renal hemodynamics in rest compared to when exposed to adenosine. This indicates that dynamic 82Rb PET/CT has potential to detect differences in renal hemodynamics in stress conditions compared to the resting state, and might be useful as a novel diagnostic tool for assessing renal perfusion. [ABSTRACT FROM AUTHOR]

Background: Yttrium‐90 (90Y$^{90}{\rm {Y}}$) represents the primary radioisotope used in radioembolization procedures, while holmium‐166 (166Ho$^{166}{\rm {Ho}}$) is hypothesized to serve as a viable substitute for 90Y$^{90}{\rm {Y}}$ due to its comparable therapeutic potential and improved quantitative imaging. Voxel‐based dosimetry for these radioisotopes relies on activity images obtained through PET or SPECT and dosimetry methods, including the voxel S‐value (VSV) and the local deposition method (LDM). However, the evaluation of the accuracy of absorbed dose calculations has been limited by the use of non‐ideal reference standards and investigations restricted to the liver. The objective of this study was to expand upon these dosimetry characterizations by investigating the impact of image resolutions, voxel sizes, target volumes, and tissue materials on the accuracy of 90Y$^{90}{\rm {Y}}$ and 166Ho$^{166}{\rm {Ho}}$ dosimetry techniques. Methods: A specialized radiopharmaceutical dosimetry software called reDoseMC was developed using the Geant4 Monte Carlo toolkit and validated by benchmarking the generated 90Y$^{90}{\rm {Y}}$ kernels with published data. The decay spectra of both 90Y$^{90}{\rm {Y}}$ and 166Ho$^{166}{\rm {Ho}}$ were also compared. Multiple VSV kernels were generated for the liver, lungs, soft tissue, and bone for isotropic voxel sizes of 1 mm, 2 mm, and 4 mm. Three theoretical phantom setups were created with 20 or 40 mm activity and mass density inserts for the same three voxel sizes. To replicate the limited spatial resolutions present in PET and SPECT images, image resolutions were modeled using a 3D Gaussian kernel with a Full Width at Half Maximum (FWHM) ranging from 0 to 16 mm and with no added noise. The VSV and LDM dosimetry methods were evaluated by characterizing their respective kernels and analyzing their absorbed dose estimates calculated on theoretical phantoms. The ground truth for these estimations was calculated using reDoseMC. Results: The decay spectra obtained through reDoseMC showed less than a 1% difference when compared to previously published experimental data for energies below 1.9 MeV in the case of 90Y$^{90}{\rm {Y}}$ and less than 1% for energies below 1.5 MeV for 166Ho$^{166}{\rm {Ho}}$. Additionally, the validation kernels for 90Y$^{90}{\rm {Y}}$ VSV exhibited results similar to those found in published Monte Carlo codes, with source dose depositions having less than a 3% error margin. Resolution thresholds (FWHMthreshs${\rm {FWHM}}_\mathrm{thresh}{\rm {s}}$), defined as resolutions that resulted in similar dose estimates between the LDM and VSV methods, were observed for 90Y$^{90}{\rm {Y}}$. They were 1.5 mm for bone, 2.5 mm for soft tissue and liver, and 8.5 mm for lungs. For 166Ho$^{166}{\rm {Ho}}$, the accuracy of absorbed dose deposition was found to be dependent on the contributions of absorbed dose from photons. Volume errors due to variations in voxel size impacted the final dose estimates. Larger target volumes yielded more accurate mean doses than smaller volumes. For both radioisotopes, the radial dose profiles for the VSV and LDM approximated but never matched the reference standard. Conclusions: reDoseMC was developed and validated for radiopharmaceutical dosimetry. The accuracy of voxel‐based dosimetry was found to vary widely with changes in image resolutions, voxel sizes, chosen target volumes, and tissue material; hence, the standardization of dosimetry protocols was found to be of great importance for comparable dosimetry analysis. [ABSTRACT FROM AUTHOR]

Background: Phantoms are commonly used to evaluate and compare the performance of imaging systems given the known ground truth. Positron emission tomography (PET) scanners are routinely validated using the NEMA image quality phantom, in which lesions are modeled using 10 to 37 mm fillable spheres. The NEMA phantom neglects, however, to model focal (3–10‐mm), high‐uptake lesions that are increasingly observed in prostate‐specific membrane antigen (PSMA) PET images. PSMA‐targeting radiopharmaceuticals allow for enhanced detection of metastatic prostate cancers. As such, there is significant need to develop an updated phantom which considers both the quantitative and lesion detectability of this new paradigm in oncological PET imaging. Purpose: In this work, we present the Quantitative PET Prostate Phantom (Q3P); a portable and modular phantom that can be used to improve and harmonize imaging protocols for 18F‐PSMA PET scans. Methods: A one‐piece cylindrical phantom was designed effectively in two halves, which we call modules. Module 1 was designed to mimic lesions in the presence of background, and Module 2 mimicked very high contrast conditions (i.e., very low background) that can be observed in 18F‐PSMA PET scans. Shell‐less radioactive spheres (3–16‐mm) were cast using epoxy resin mixed with sodium‐22 (22Na), a long half‐life positron emitter with positron range similar to 18F. To establish realistic lesion contrast, the 22Na spheres were mounted in a cylindrical chamber that can be filled with an 18F background (module 1). Thirteen exchangeable spherical cavity inserts (3–37‐mm) were machined in two parts and solvent welded together, and filled with 18F (50 kBq/mL) to model lesions with very high contrast (module 2). Five 2.5‐min PET scans were acquired on a 5‐ring GE Discovery MI PET/CT scanner (General Electric, USA). Lesions were segmented using 41% of SUVmax fixed thresholding (41% FT) and recovery coefficients (RCs) were computed from 5 noise realizations. Results: The manufactured phantom is portable (5.7 kg) and scan preparation takes less than 40 min. The total 22Na activity is 250 kBq, allowing it to be shipped as an exempt package under International Atomic Energy Agency (IAEA) regulations. Recovery coefficients, computed using PSF modeling and no post‐reconstruction smoothing, were 130.3% (16 mm), 147.1% (10 mm), 87.2% (6 mm), and 7.0% (3 mm) for RCmax, which decreased to 91.1% (16 mm), 90.6% (10 mm), 53.2% (6 mm), and 3.6% (3 mm) for RCmean in the 22Na spheres. Comparatively, 18F sphere recovery was 110.7% (17 mm), 123.6% (10 mm), 106.5% (7 mm), and 23.3% (3 mm) for RCmax, which was reduced to 76.7% (17 mm), 77.7% (10 mm), 66.8% (7 mm), and 13.5% (3 mm), for RCmean. Conclusions: A standardized imaging phantom was developed for lesion quantification assessment in 18F‐PSMA PET images. The phantom is configurable, providing users with the opportunity to modify background activity levels or sphere sizes according to clinical demands. Distributed to the community, the Q3P phantom has the potential to enable better assessment of lesion quantification and harmonization of 18F‐PSMA PET imaging, which may lead to more robust predictive metrics and better outcome prediction in metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease is the most common cause of death worldwide, including infection and inflammation related conditions. Multiple studies have demonstrated potential advantages of hybrid positron emission tomography combined with computed tomography (PET/CT) as an adjunct to current clinical inflammatory and infectious biochemical markers. To quantitatively analyze vascular diseases at PET/CT, robust segmentation of the aorta is necessary. However, manual segmentation is extremely time‐consuming and labor‐intensive. Purpose: To investigate the feasibility and accuracy of an automated tool to segment and quantify multiple parts of the diseased aorta on unenhanced low‐dose computed tomography (LDCT) as an anatomical reference for PET‐assessed vascular disease. Methods: A software pipeline was developed including automated segmentation using a 3D U‐Net, calcium scoring, PET uptake quantification, background measurement, radiomics feature extraction, and 2D surface visualization of vessel wall calcium and tracer uptake distribution. To train the 3D U‐Net, 352 non‐contrast LDCTs from (2‐[18F]FDG and Na[18F]F) PET/CTs performed in patients with various vascular pathologies with manual segmentation of the ascending aorta, aortic arch, descending aorta, and abdominal aorta were used. The last 22 consecutive scans were used as a hold‐out internal test set. The remaining dataset was randomly split into training (n = 264; 80%) and validation (n = 66; 20%) sets. Further evaluation was performed on an external test set of 49 PET/CTs. The dice similarity coefficient (DSC) and Hausdorff distance (HD) were used to assess segmentation performance. Automatically obtained calcium scores and uptake values were compared with manual scoring obtained using clinical softwares (syngo.via and Affinity Viewer) in six patient images. intraclass correlation coefficients (ICC) were calculated to validate calcium and uptake values. Results: Fully automated segmentation of the aorta using a 3D U‐Net was feasible in LDCT obtained from PET/CT scans. The external test set yielded a DSC of 0.867 ± 0.030 and HD of 1.0 [0.6–1.4] mm, similar to an open‐source model with a DSC of 0.864 ± 0.023 and HD of 1.4 [1.0–1.8] mm. Quantification of calcium and uptake values were in excellent agreement with clinical software (ICC: 1.00 [1.00–1.00] and 0.99 [0.93–1.00] for calcium and uptake values, respectively). Conclusions: We present an automated pipeline to segment the ascending aorta, aortic arch, descending aorta, and abdominal aorta on LDCT from PET/CT and to accurately provide uptake values, calcium scores, background measurement, radiomics features, and a 2D visualization. We call this algorithm SEQUOIA (SEgmentation, QUantification, and visualizatiOn of the dIseased Aorta) and is available at https://github.com/UMCG‐CVI/SEQUOIA. This model could augment the utility of aortic evaluation at PET/CT studies tremendously, irrespective of the tracer, and potentially provide fast and reliable quantification of cardiovascular diseases in clinical practice, both for primary diagnosis and disease monitoring. [ABSTRACT FROM AUTHOR]

18F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) is considered an accurate diagnostic tool to determine whole-body endocrine responsiveness. In the endocrine therapy (ET)-FES trial, we evaluated 18F-FES PET/CT as a predictive tool in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). Eligible patients underwent an 18F-FES PET/CT at baseline. Patients with standardized uptake value (SUV) ≥ 2 received single-agent ET until progressive disease; patients with SUV < 2 were randomized to single-agent ET (arm A) or chemotherapy (ChT) (arm B). The primary objective was to compare the activity of first-line ET versus ChT in patients with 18F-FES SUV < 2. Overall, 147 patients were enrolled; 117 presented with 18F-FES SUV ≥ 2 and received ET; 30 patients with SUV < 2 were randomized to ET or ChT. After a median follow-up of 62.4 months, 104 patients (73.2%) had disease progression and 53 died (37.3%). Median progression-free survival (PFS) was 12.4 months [95% confidence interval (CI) 3.1-59.6 months] in patients with SUV < 2 randomized to arm A versus 23.0 months (95% CI 7.7-30.0 months) in arm B, [hazard (HR) = 0.71, 95% CI 0.3-1.7 months]; median PFS was 18.0 months (95% CI 11.2-23.1 months) in patients with SUV ≥ 2 treated with ET. Median overall survival (OS) was 28.2 months (95% CI 14.2 months-not estimable) in patients with SUV < 2 randomized to ET (arm A) versus 52.8 months (95% CI 16.2 months-not estimable) in arm B (ChT). Median OS was not reached in patients with SUV ≥ 2. 60-month OS rate was 41.6% (95% CI 10.4% to 71.1%) in arm A, 42.0% (95% CI 14.0% to 68.2%) in arm B, and 59.6% (95% CI 48.6% to 69.0%) in patients with SUV ≥ 2. In patients with SUV ≥ 2, 60-month OS rate was 72.6% if treated with aromatase inhibitors (AIs) versus 40.6% in case of fulvestrant or tamoxifen (P < 0.005). The ET-FES trial demonstrated that ER+/HER2− MBC patients are a heterogeneous population, with different levels of endocrine responsiveness based on 18F-FES CT/PET SUV. • 18F-FES PET/CT may be used as a predictive tool of efficacy of ET to assess overall endocrine sensitivity. • Endocrine-sensitive patients (SUVmax ≥ 2) treated with single-agent ET have a prolonged OS. • In endocrine-sensitive patients, PFS and OS related to the use of AI were significantly higher than ER-directed agents. • 18F-FES PET/CT can be used as a valid alternative to biopsy. [ABSTRACT FROM AUTHOR]

Detection and measurement of amyloid‐beta (Aβ) in the brain is a key factor for early identification and diagnosis of Alzheimer's disease (AD). We aimed to develop a deep learning model to predict Aβ cerebrospinal fluid (CSF) concentration directly from amyloid PET images, independent of tracers, brain reference regions or preselected regions of interest. We used 1870 Aβ PET images and CSF measurements to train and validate a convolutional neural network ("ArcheD"). We evaluated the ArcheD performance in relation to episodic memory and the standardized uptake value ratio (SUVR) of cortical Aβ. We also compared the brain region's relevance for the model's CSF prediction within clinical‐based and biological‐based classifications. ArcheD‐predicted Aβ CSF values correlated with measured Aβ CSF values (r = 0.92; q < 0.01), SUVR (rAV45 = −0.64, rFBB = −0.69; q < 0.01) and episodic memory measures (0.33 < r < 0.44; q < 0.01). For both classifications, cerebral white matter significantly contributed to CSF prediction (q < 0.01), specifically in non‐symptomatic and early stages of AD. However, in late‐stage disease, the brain stem, subcortical areas, cortical lobes, limbic lobe and basal forebrain made more significant contributions (q < 0.01). Considering cortical grey matter separately, the parietal lobe was the strongest predictor of CSF amyloid levels in those with prodromal or early AD, while the temporal lobe played a more crucial role for those with AD. In summary, ArcheD reliably predicted Aβ CSF concentration from Aβ PET scans, offering potential clinical utility for Aβ level determination. [ABSTRACT FROM AUTHOR]

In this study, 89Zr-DFO-Cetuximab was prepared under the optimized conditions with a radiochemical purity > 99%, and a specific activity of 185 GBq g−1. Cellular studies on EGFR + SW480 colon cancer and EGFR-CHO cell lines were performed, indicating the remarkable capability of 89Zr-DFO-Cetuximab for binding to the low EGFR-expressing cells. High accumulation was observed in tumors of nude mice-bearing SW480 cell lines. Human absorbed dose estimation showed the liver receives the highest absorbed dose (0.94 mGy MBq−1). This radiopharmaceutical is the suitable PET agent for imaging of EGFR-expressing tumors at 72–120 h after injection. [ABSTRACT FROM AUTHOR]

The limitations of current imaging methods to detect small or superficial endometriotic lesions prompt the search for new molecular targets. TSPO is an 18 KDa protein located in the outer mitochondrial membrane, which can be traced by positron emission tomography (PET) using specific ligands. TSPO is located mostly in neurons and inflammatory sites outside the brain. We hypothesized that it might also be expressed in the human endometrium and endometrial‐like tissue, being a target for molecular imaging of endometriosis. This prospective cross‐sectional study included 28 women with endometriosis and 11 endometriosis‐free controls. Endometriotic lesions (n = 49) and normal peritoneum (n = 13) from endometriosis patients were obtained during laparoscopy, while samples of eutopic endometrium from patients with endometriosis (n = 28) and from control women (n = 11) were collected in the operating room using a flexible device. TSPO mRNA expression was evaluated by quantitative reverse‐transcription real‐time PCR while protein expression was evaluated by immunohistochemistry with a monoclonal antibody antihuman TSPO. TSPO mRNA expression was detected in an invariable fashion in all tissue types evaluated; however, TSPO protein was found to be more abundant in the glandular epithelium than in the stroma, both in the endometrium and in the endometriotic lesions. Interestingly, hormone therapies did not alter the expression of TSPO, and its presence was mostly negative in tissues adjacent to endometriotic implants. As a proof of concept, the protein expression pattern of TSPO in endometriotic tissue and along the adjacent areas suggests that TSPO‐based molecular imaging might be used for noninvasive endometriosis detection. [ABSTRACT FROM AUTHOR]

Background: Spinocerebellar ataxia 17 (SCA17) is a rare autosomal dominant form of inherited ataxia, caused by heterozygous trinucleotide repeat expansions encoding glutamine in the TATA box-binding protein (TBP) gene. Case description: We describe the clinical history, neuropsychological, and neuroimaging findings of a 42-year-old patient who presented for medical attention showing prevalent behavioral and cognitive problems along with progressively worsening gait disturbances. The patient's family history indicated the presence of SCA17 in the maternal lineage. Genetic analysis confirmed a heterozygous 52-CAG pathological expansion repeat in TBP (normal interval, 25–40 CAG. Brain 18-fluorodeoxyglucose positron emission tomography (FDG-PET) showed bilateral hypometabolism in the sensorimotor cortex, with a slight predominance on the right, as well as in the striatal nuclei and thalamic hypermetabolism, a finding similar to what is observed in Huntington's disease. The patient also underwent neuropsychological evaluation, which revealed mild cognitive impairment and difficulties in social interaction and understanding other's emotions (Faux Pas Test and Reading the Mind in the Eyes Test). Conclusion: Our report emphasizes the importance of considering SCA17 as a possible diagnosis in patients with a prevalent progressive cognitive and behavioral disorders, even with a pattern of FDG-PET hypometabolism not primarily indicative of this disease. [ABSTRACT FROM AUTHOR]

This document is a survey conducted by the European Association of Nuclear Medicine (EANM) and the European Association of Cardiovascular Imaging (EACVI) on the use of nuclear medicine in diagnosing cardiac sarcoidosis and amyloidosis. Both conditions are often underdiagnosed and traditionally diagnosed through invasive procedures. However, imaging techniques such as echocardiography, cardiovascular magnetic resonance (CMR), and nuclear imaging are increasingly being used. The survey found that while nuclear imaging is recommended for these conditions, it is not widely used due to factors such as lack of equipment and alternative imaging techniques. Standardization and collaboration are needed to optimize the use of nuclear medicine imaging in clinical practice. [Extracted from the article]

Epilepsy is one of the most frequent neurological conditions with an estimated prevalence of more than 50 million people worldwide and an annual incidence of two million. Although pharmacotherapy with anti-seizure medication (ASM) is the treatment of choice, ~30% of patients with epilepsy do not respond to ASM and become drug resistant. Focal epilepsy is the most frequent form of epilepsy. In patients with drug-resistant focal epilepsy, epilepsy surgery is a treatment option depending on the localisation of the seizure focus for seizure relief or seizure freedom with consecutive improvement in quality of life. Beside examinations such as scalp video/electroencephalography (EEG) telemetry, structural, and functional magnetic resonance imaging (MRI), which are primary standard tools for the diagnostic work-up and therapy management of epilepsy patients, molecular neuroimaging using different radiopharmaceuticals with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) influences and impacts on therapy decisions. To date, there are no literature-based praxis recommendations for the use of Nuclear Medicine (NM) imaging procedures in epilepsy. The aims of these guidelines are to assist in understanding the role and challenges of radiotracer imaging for epilepsy; to provide practical information for performing different molecular imaging procedures for epilepsy; and to provide an algorithm for selecting the most appropriate imaging procedures in specific clinical situations based on current literature. These guidelines are written and authorized by the European Association of Nuclear Medicine (EANM) to promote optimal epilepsy imaging, especially in the presurgical setting in children, adolescents, and adults with focal epilepsy. They will assist NM healthcare professionals and also specialists such as Neurologists, Neurophysiologists, Neurosurgeons, Psychiatrists, Psychologists, and others involved in epilepsy management in the detection and interpretation of epileptic seizure onset zone (SOZ) for further treatment decision. The information provided should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals and imaging modalities. [ABSTRACT FROM AUTHOR]

The 36th EANM Annual Congress in Vienna, Austria brought together healthcare professionals, researchers, and industry representatives to discuss advancements in nuclear medicine. The congress featured scientific talks and exhibitions, with a focus on oncology. Studies presented at the conference explored the use of different PET tracers for prostate, breast, and rectal cancer, as well as the potential of plasma biomarkers in neurodegenerative diseases. Other topics included the identification of epileptogenic zones in children, changes in brain networks during aging, and new PET tracers for coronary artery disease. These studies contribute to the understanding and treatment of various diseases in the field of nuclear medicine. [Extracted from the article]

Purpose: Long axial field-of-view (LAFOV) positron emission tomography (PET) systems allow to image all major organs with one bed position, which is particularly useful for acquiring whole-body dynamic data using short-lived radioisotopes like 82Rb. Methods: We determined the absorbed dose in target organs of three subjects (29, 40, and 57 years old) using two different methods, i.e., MIRD and voxel dosimetry. The subjects were injected with 407.0 to 419.61 MBq of [82Rb]Cl and were scanned dynamically for 7 min with a LAFOV PET/CT scanner. Results: Using the MIRD formalism and voxel dosimetry, the absorbed dose ranged from 1.84 to 2.78 μGy/MBq (1.57 to 3.92 μGy/MBq for voxel dosimetry) for the heart wall, 2.76 to 5.73 μGy/MBq (3.22 to 5.37 μGy/MBq for voxel dosimetry) for the kidneys, and 0.94 to 1.88 μGy/MBq (0.98 to 1.92 μGy/MBq for voxel dosimetry) for the lungs. The total body effective dose lied between 0.50 and 0.76 μSv/MBq. Conclusion: Our study suggests that the radiation dose associated with [82Rb]Cl PET/CT can be assessed by means of dynamic LAFOV PET and that it is lower compared to literature values. [ABSTRACT FROM AUTHOR]

Background: Hodgkin lymphoma (HL) in pediatric populations has a high survival rate but poses risks for long-term morbidities. Although [18F]fluoro‑2‑deoxy‑2‑d‑glucose positron emission tomography ([18F]FDG PET) scans offer potential for improved risk stratification, the definitive prognostic value of quantitative [18F]FDG PET parameters remains unclear for pediatric HL. Methods: A single-center, retrospective study included pediatric patients diagnosed with HL between 2016 and 2023 treated according to EuroNet-PHL-C1 and DAL/GPOH-HD protocols. Patients underwent baseline and interim PET/CT scans after two chemotherapy cycles. Event-free survival (EFS) was the primary endpoint, Deauville score was the secondary endpoint. Quantitative [18F]FDG PET parameters included SUVmax, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) that were evaluated using two segmentation methods (SUV 2.5, 41% SUVmax). Survival outcomes were assessed using Cox regression analysis. Results: A total of 115 patients (50 males, median age 14.2 years) were studied, with a median follow-up period of 35 months. During this period, 16 cases (13.9%) of relapse or progression were noted. Baseline and interim MTV 2.5, MTV 41%, TLG 2.5, and TLG 41%, along with interim SUVmax, were significantly associated with worse EFS and correlated with post-treatment Deauville scores. In multivariable analysis, interim MTV 2.5 > 0 ml (adj. hazard ratio, HR: 3.89, p = 0.009) and interim TLG 41% ≥ 30 g (adj. HR: 7.98, p = 0.006) were independent risk factors for EFS. Conclusion: Baseline and interim [18F]FDG PET parameters can serve as significant prognostic indicators for EFS and treatment response in pediatric HL. These quantitative measures could enhance individualized, risk-adapted treatment strategies for children and adolescents with HL. [ABSTRACT FROM AUTHOR]

Purpose: Evaluation of 90Y liver radioembolization post-treatment clinical data using a whole-body Biograph Vision Quadra PET/CT to investigate the potential of protocol optimization in terms of scan time and dosimetry. Methods: 17 patients with hepatocellular carcinoma with median (IQR) injected activity 2393 (1348–3298) MBq were included. Pre-treatment dosimetry plan was based on 99mTc-MAA SPECT/CT with Simplicit90Y™ and post-treatment validation with Quadra using Simplicit90Y™ and HERMIA independently. Regarding the image analysis, mean and peak SNR, the coefficient of variation (COV) and lesion-to-background ratio (LBR) were evaluated. For the post-treatment dosimetry validation, the mean tumor, whole liver and lung absorbed dose evaluation was performed using Simplicit90Y and HERMES. Images were reconstructed with 20-, 15-, 10-, 5- and 1- min sinograms with 2, 4, 6 and 8 iterations. Wilcoxon signed rank test was used to show statistical significance (p < 0.05). Results: There was no difference of statistical significance between 20- and 5- min reconstructed times for the peak SNR, COV and LBR. In addition, there was no difference of statistical significance between 20- and 1- min reconstructed times for all dosimetry metrics. Lung dosimetry showed consistently lower values than the expected. Tumor absorbed dose based on Simplicit90Y™ was similar to the expected while HERMES consistently underestimated significantly the measured tumor absorbed dose. Finally, there was no difference of statistical significance between expected and measured tumor, whole liver and lung dose for all reconstruction times. Conclusion: In this study we evaluated, in terms of image quality and dosimetry, whole-body PET clinical images of patients after having been treated with 90Y microspheres radioembolization for liver cancer. Compared to the 20-min standard scan, the simulated 5-min reconstructed images provided equal image peak SNR and noise behavior, while performing also similarly for post-treatment dosimetry of tumor, whole liver and lung absorbed doses. [ABSTRACT FROM AUTHOR]

Purpose: Accurately and early detection of intestinal fibrosis in Crohn's disease (CD) is crucial for clinical management yet remains an unmet need. Fibroblast activation protein inhibitor (FAPI) PET/CT has emerged as a promising tool to assess fibrosis. We aimed to investigate the diagnostic capability of [18F]F-FAPI PET/CT in detecting intestinal fibrosis and compared it with[18F]F-FDG PET/CT and magnetization transfer MR imaging (MTI). Methods: Twenty-two rats underwent TNBS treatment to simulate fibrosis development, followed by three quantitative imaging sessions within one week. Mean and maximum standardized uptake values (SUVmean and SUVmax) were calculated on[18F]F-FAPI and [18F]F-FDG PET/CT, along with normalized magnetization transfer ratio on MTI. Intestinal fibrosis was assessed pathologically, with MTI serving as imaging standard for fibrosis. The diagnostic efficacy of imaging parameters in fibrosis was compared using pathological and imaging standards. Ten patients with 34 bowel strictures were prospectively recruited to validate their diagnostic performance, using the identical imaging protocol. Results: In CD patients, the accuracy of FAPI uptake (both AUCs = 0.87, both P ≤ 0.01) in distinguishing non-to-mild from moderate-to-severe fibrosis was higher than FDG uptake (both AUCs = 0.82, P ≤ 0.01) and comparable to MTI (AUCs = 0.90, P ≤ 0.001). In rats, FAPI uptake responded earlier to fibrosis development than FDG and MTI; consistently, during early phase, FAPI uptake showed a stronger correlation (SUVmean: R = 0.69) with pathological fibrosis than FDG (SUVmean: R = 0.17) and MTI (R = 0.52). Conclusion: The diagnostic efficacy of [18F]F-FAPI PET/CT in detecting CD fibrosis is superior to [18F]F-FDG PET/CT and comparable to MTI, exhibiting great potential for early detection of intestinal fibrosis. [ABSTRACT FROM AUTHOR]

Purpose: High blood glucose (hBG) in patients undergoing [18F]FDG PET/CT scans often results in rescheduling the examination, which may lead to clinical delay for the patient and decrease productivity for the department. The aim of this study was to evaluate whether long-axial field-of-view (LAFOV) PET/CT can minimize the effect of altered bio-distribution in hBG patients and is able to provide diagnostic image quality in hBG situations. Materials and methods: Oncologic patients with elevated blood glucose (≥ 8.0 mmol/l) and normal blood glucose (< 8.0 mmol/l, nBG) levels were matched for tumor entity, gender, age, and BMI. hBG patients were further subdivided into two groups (BG 8–11 mmol/l and BG > 11 mmol/l). Tracer uptake in the liver, muscle, and tumor was evaluated. Furthermore, image quality was compared between long acquisitions (ultra-high sensitivity mode, 360 s) on a LAFOV PET/CT and routine acquisitions equivalent to a short-axial field-of-view scanner (simulated (sSAFOV), obtained with high sensitivity mode, 120 s). Tumor-to-background ratio (TBR) and contrast-to-noise ratio (CNR) were used as the main image quality criteria. Results: Thirty-one hBG patients met the inclusion criteria and were matched with 31 nBG patients. Overall, liver uptake was significantly higher in hBG patients (SUVmean, 3.07 ± 0.41 vs. 2.37 ± 0.33; p = 0.03), and brain uptake was significantly lower (SUVmax, 7.58 ± 0.74 vs. 13.38 ± 3.94; p < 0.001), whereas muscle (shoulder/gluteal) uptake showed no statistically significant difference. Tumor uptake was lower in hBG patients, resulting in a significantly lower TBR in the hBG cohort (3.48 ± 0.74 vs. 5.29 ± 1.48, p < 0.001). CNR was higher in nBG compared to hBG patients (12.17 ± 4.86 vs. 23.31 ± 12.22, p < 0.001). However, subgroup analysis of nBG 8–11 mmol/l on sSAFOV PET/CT compared to hBG (> 11 mmol/l) patients examined with LAFOV PET/CT showed no statistical significant difference in CNR (19.84 ± 8.40 vs. 17.79 ± 9.3, p = 0.08). Conclusion: While elevated blood glucose (> 11 mmol) negatively affected TBR and CNR in our cohort, the images from a LAFOV PET-scanner had comparable CNR to PET-images acquired from nBG patients using sSAFOV PET/CT. Therefore, we argue that oncologic patients with increased blood sugar levels might be imaged safely with LAFOV PET/CT when rescheduling is not feasible. [ABSTRACT FROM AUTHOR]

Purpose: We hypothesized that severe tau burden in brain regions involved in direct or indirect pathways of the basal ganglia correlate with more severe striatal dopamine deficiency in four-repeat (4R) tauopathies. Therefore, we correlated [18F]PI-2620 tau-positron-emission-tomography (PET) imaging with [123I]-Ioflupane single-photon-emission-computed tomography (SPECT) for dopamine transporter (DaT) availability. Methods: Thirty-eight patients with clinically diagnosed 4R-tauopathies (21 male; 69.0 ± 8.5 years) and 15 patients with clinically diagnosed α-synucleinopathies (8 male; 66.1 ± 10.3 years) who underwent [18F]PI-2620 tau-PET and DaT-SPECT imaging with a time gap of 3 ± 5 months were evaluated. Regional Tau-PET signals and DaT availability as well as their principal components were correlated in patients with 4R-tauopathies and α-synucleinopathies. Both biomarkers and the residuals of their association were correlated with clinical severity scores in 4R-tauopathies. Results: In patients with 4R-tauopathies, [18F]PI-2620 binding in basal ganglia and midbrain regions was negatively associated with striatal DaT availability (i.e. globus pallidus internus and putamen (β = − 0.464, p = 0.006, Durbin-Watson statistics = 1.824) in a multiple regression model. Contrarily, [18F]PI-2620 binding in the dentate nucleus showed no significant regression factor with DaT availability in the striatum (β = 0.078, p = 0.662, Durbin-Watson statistics = 1.686). Patients with α-synucleinopathies did not indicate any regional associations between [18F]PI-2620-binding and DaT availability. Higher DaT-SPECT binding relative to tau burden was associated with better clinical performance (β = − 0.522, p = 0.011, Durbin-Watson statistics = 2.663) in patients with 4R-tauopathies. Conclusion: Tau burden in brain regions involved in dopaminergic pathways is associated with aggravated dopaminergic dysfunction in patients with clinically diagnosed primary tauopathies. The ability to sustain dopamine transmission despite tau accumulation may preserve motor function. [ABSTRACT FROM AUTHOR]

Background: Fibroblast activation protein (FAP) has emerged as a promising target for diagnosis and therapeutic intervention due to high expression and accumulation in the stromal compartments of a variety of malignant tumors. FAP-2286 utilizes cyclic peptides with FAP-binding characteristics to enhance the retention of the imaging agent within tumors, in contrast to the small-molecule FAP inhibitors (FAPI) like FAPI-04/46. The aim of this study was to quantify the tumor uptake of [68Ga] Gallium-FAP-2286 within primary solid tumors, adjacent excised tissues, and metastatic lesions. Methods: In this prospective study, 21 patients (average age 51.9) with various diagnoses of remaining and metastatic cancers participated. Among them, six had metastatic sarcoma, and 14 had adenocarcinoma, including eight breast, two rectum, two lung, two pancreas, and one thyroid cases. The patients underwent a [68Ga]Ga-FAP-2286 PET/CT scan. An hour post-administration of [68Ga]Ga-FAP-2286, a visual assessment of whole body scans and semi-quantification of the PET/CT results were carried out. The standardized uptake values (SUV)max of [68Ga]Ga-FAP-2286 in tumor lesions and the tumor-to-background ratio (TBR) were then calculated. Results: The vital signs of the patients, such as heart rate, blood pressure, and temperature, were observed before, during, and after the diagnostic procedure during the 4-h follow-up. All individuals underwent the [68Ga]Ga-FAP-2286 PET/CT scans without any signs of drug-associated pharmacological effects. The PET/CT scans displayed substantial absorption of [68Ga]Ga-FAP-2286 in tumor lesions in all patients (100% (21/21)). Irrespective of the tumors' origins (epithelial or mesothelium) and whether they exhibited local recurrence, distant recurrence, or metastatic lesions, the PET/CT scans revealed the uptake of [68Ga]Ga-FAP-2286 in these lesions. Conclusion: Overall, these data suggest that [68Ga]Ga-FAP-2286 is a promising FAP derivative for efficient metastatic cancer diagnosis and being considered as a potential compound for therapeutic application in patients with advanced metastatic cancers. [ABSTRACT FROM AUTHOR]

Purpose: Neuropilin-1 (NRP-1) is a multifunctional protein involved in a variety of biological processes such as angiogenesis, tumorigenesis and immunomodulation. It was usually overexpressed in many cancer cell lines and correlated with poor prognosis of breast cancer. Positron emission tomography (PET) is an advanced imaging technique for detecting the function and metabolism of tumor-associated molecules in real time, dynamically, quantitatively and noninvasively. To improve the level of early diagnosis and evaluate the prognosis of breast cancer, an NRP-1 targeting peptide-based tracer [68 Ga]Ga-NOTA-PEG4-CK2 was designed to sensitively and specifically detect the NRP-1 expression in vivo via PET imaging. Methods: In silico modeling and microscale thermophoresis (MST) assay were carried out to design the NRP-1 targeting peptide NOTA-PEG4-CK2, and it was further radiolabeled with 68 Ga to prepare the tracer [68 Ga]Ga-NOTA-PEG4-CK2. The radiochemical yield (RCY), radiochemical purity (RCP), molar activity (Am), lipid-water partition coefficient (Log P) and stability of [68 Ga]Ga-NOTA-PEG4-CK2 were assessed. The targeting specificity of the tracer for NRP-1 was investigated by in vitro cellular uptake assay and in vivo PET imaging as well as blocking studies. The sensitivity of the tracer in monitoring the dynamic changes of NRP-1 expression induced by chemical drug was also investigated in vitro and in vivo. Ex vivo biodistribution, autoradiography, western blot, and immunofluorescence staining were also performed to study the specificity of [68 Ga]Ga-NOTA-PEG4-CK2 for NRP-1. Results: [68 Ga]Ga-NOTA-PEG4-CK2 was designed and synthesized with high RCY (> 98%), high stability (RCP > 95%) and high affinity to NRP-1 (KD = 25.39 ± 1.65 nM). In vitro cellular uptake assay showed that the tracer [68 Ga]Ga-NOTA-PEG4-CK2 can specifically bind to NRP-1 positive cancer cells MDA-MB-231 (1.04 ± 0.04% at 2 h) rather than NRP-1 negative cancer cells NCI-H1299 (0.43 ± 0.05%). In vivo PET imaging showed the maximum tumor uptake of [68 Ga]Ga-NOTA-PEG4-CK2 in MDA-MB-231 xenografts (4.16 ± 0.67%ID/mL) was significantly higher than that in NCI-H1299 xenografts (1.03 ± 0.19%ID/mL) at 10 min post injection, and the former exhibited higher tumor-to-muscle uptake ratio (5.22 ± 0.18) than the latter (1.07 ± 0.27) at 60 min post injection. MDA-MB-231 xenografts pretreated with nonradioactive precursor NOTA-PEG4-CK2 showed little tumor uptake of [68 Ga]Ga-NOTA-PEG4-CK2 (1.67 ± 0.38%ID/mL at 10 min post injection). Both cellular uptake assay and PET imaging revealed that NRP-1 expression in breast cancer MDA-MB-231 could be effectively suppressed by SB-203580 treatment and can be sensitively detected by [68 Ga]Ga-NOTA-PEG4-CK2. Ex vivo analysis also proved the high specificity and sensitivity of [68 Ga]Ga-NOTA-PEG4-CK2 for NRP-1 expression in MDA-MB-231 xenografts. Conclusion: A promising NRP-1 targeting PET tracer [68 Ga]Ga-NOTA-PEG4-CK2 was successfully prepared. It showed remarkable specificity and sensitivity in monitoring the dynamic changes of NRP-1 expression. Hence, it could provide valuable information for early diagnosis of NRP-1 relevant cancers and evaluating the prognosis of cancer patients. A novel promising NRP-1 targeting PET tracer [68 Ga]Ga-NOTA-PEG4-CK2 was developed based on a series of in vitro and in vivo investigations. The tracer showed remarkable specificity and sensitivity in detecting the expression of NRP-1. It could be applied for noninvasively and dynamically monitoring the NRP-1 expression in tumors and predicting the prognosis of breast cancer. [ABSTRACT FROM AUTHOR]

Integrin receptor αvβ3 and gastrin-releasing peptide receptor (GRPR) expression of tumors could be detected using PET imaging with radiolabeled Arg-Gly-Asp (RGD) and the antagonistic bombesin analog RM26, respectively. The purpose of this study was to investigate the dual receptor-targeting property of the heterodimer RGD-RM26-03 (denoted as LNC1015), demonstrate the tumor diagnostic value of [68Ga]Ga-LNC1015 in preclinical experiments, and evaluate its preliminary clinical feasibility. Methods: LNC1015 was designed and synthesized by linking cyclic RGD and the RM26 peptide. Preclinical pharmacokinetics were detected in a PC3 xenograft model using microPET and biodistribution studies. The clinical feasibility of [68Ga]Ga-LNC1015 PET/CT was performed in patients with breast cancer, and the results were compared with those of 18F-fluorodeoxyglucose (FDG). Results: [68Ga]Ga-LNC1015 had good stability in saline for at least 2 h, and favorable binding affinity and specificity were demonstrated in vitro and in vivo. The tumor uptake and retention of [68Ga]Ga-LNC1015 during PET imaging were improved compared with its monomeric counterparts [68Ga]Ga-RGD and [68Ga]Ga-RM26 at all the time points examined. In our initial clinical studies, the tumor uptake and tumor-to-background ratio (TBR) of primary and metastatic lesions in [68Ga]Ga-LNC1015 PET/CT were significantly higher than those in [18F]FDG PET/CT, resulting in high lesion detection rate and tumor delineation. Conclusion: The dual targeting radiotracer [68Ga]Ga-LNC1015 showed significantly improved tumor uptake and retention, as well as lower liver uptake than [68Ga]Ga-RGD and [68Ga]Ga-RM26 monomer. The first-in-human study showed high TBRs in patients, suggesting favorable pharmacokinetics and high clinical feasibility for PET/CT imaging of cancer. [ABSTRACT FROM AUTHOR]

Purpose: Epidemiological and logistical reasons are slowing the clinical validation of the molecular imaging biomarkers in the initial stages of neurocognitive disorders. We provide an updated systematic review of the recent advances (2017–2022), highlighting methodological shortcomings. Methods: Studies reporting the diagnostic accuracy values of the molecular imaging techniques (i.e., amyloid-, tau-, [18F]FDG-PETs, DaT-SPECT, and cardiac [123I]-MIBG scintigraphy) in predicting progression from mild cognitive impairment (MCI) to dementia were selected according to the Preferred Reporting Items for a Systematic Review and Meta-Analysis (PRISMA) method and evaluated with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Main eligibility criteria were as follows: (1) ≥ 50 subjects with MCI, (2) follow-up ≥ 3 years, (3) gold standard: progression to dementia or diagnosis on pathology, and (4) measures of prospective accuracy. Results: Sensitivity (SE) and specificity (SP) in predicting progression to dementia, mainly to Alzheimer's dementia were 43–100% and 63–94% for [18F]FDG-PET and 64–94% and 48–93% for amyloid-PET. Longitudinal studies were lacking for less common disorders (Dementia with Lewy bodies-DLB and Frontotemporal lobe degeneration-FTLD) and for tau-PET, DaT-SPECT, and [123I]-MIBG scintigraphy. Therefore, the accuracy values from cross-sectional studies in a smaller sample of subjects (n > 20, also including mild dementia stage) were chosen as surrogate outcomes. DaT-SPECT showed 47–100% SE and 71–100% SP in differentiating Lewy body disease (LBD) from non-LBD conditions; tau-PET: 88% SE and 100% SP in differentiating DLB from Posterior Cortical Atrophy. [123I]-MIBG scintigraphy differentiated LBD from non-LBD conditions with 47–100% SE and 71–100% SP. Conclusion: Molecular imaging has a moderate-to-good accuracy in predicting the progression of MCI to Alzheimer's dementia. Longitudinal studies are sparse in non-AD conditions, requiring additional efforts in these settings. [ABSTRACT FROM AUTHOR]

Purpose: To develop a nuclear medicine specific patient journey audit tool (PJAT) to survey and audit patient journeys in a nuclear medicine department such as staff interaction with patients, equipment, quality of imaging and laboratory procedures, patient protection, infection control and radiation safety, with a view to optimising patient care and providing a high-quality nuclear medicine service. Methods: The PJAT was developed specifically for use in nuclear medicine practices. Thirty-two questions were formulated in the PJAT to test the department's compliance to the Australian National Safety and Quality Health Service Standards, namely clinical governance, partnering with consumers, preventing and controlling health care infection, medication safety, comprehensive care, communicating for safety, blood management and recognising and responding to acute deterioration. The PJAT was also designed to test our department's adherence to diagnostic reference levels (DRL). A total of 60 patient journey audits were completed for patients presenting for nuclear medicine, positron emission tomography and bone mineral density procedures during a consecutive 4-week period to audit the range of procedures performed. A further 120 audits were captured for common procedures in nuclear medicine and positron emission tomography during the same period. Thus, a total of 180 audits were completed. A subset of 12 patients who presented for blood labelling procedures were audited to solely assess the blood management standard. Results: The audits demonstrated over 85% compliance for the Australian national health standards. One hundred percent compliance was noted for critical aspects such as correct patient identification for the correct procedure prior to radiopharmaceutical administration, adherence to prescribed dose limits and distribution of the report within 24 h of completion of the imaging procedure. Conclusion: This PJAT can be applied in nuclear medicine departments to enhance quality programmes and patient care. Austin Health has collaborated with the IAEA to formulate the IAEA PJAT, which is now available globally for nuclear medicine departments to survey patient journeys. [ABSTRACT FROM AUTHOR]

Purpose: Fibroblast-activated protein (FAP) is highly expressed in cancer-associated fibroblasts (CAFs) of many solid cancers, but low or absent in normal tissues. Our study aimed to develop a novel FAP-specific tracer, namely [18F]FAP-2286, and evaluated its performance in comparison with well-established agents such as [18F]FAPI-42 and [68Ga]Ga-FAP-2286 in preclinical research, as well as 2-[18F]FDG in pilot clinical study. Methods: [18F]FAP-2286 was manually synthesized in accordance with Good Manufacturing Practice (GMP). Subsequent investigations encompassed cell uptake, competitive binding affinity, internalization and efflux assays using HT-1080hFAP cell lines. PET imaging and biodistribution studies were conducted in HEK-293ThFAP, A549hFAP, HT-1080hFAP tumor-bearing mice as well as HEK-293T, A549 and HT-1080 control groups. Furthermore, clinical evaluation of [18F]FAP-2286 was performed in fifteen patients with various cancers compared to 2-[18F]FDG PET. Results: The radiolabeling yield of [18F]FAP-2286 was 30.53 ± 5.20%, with a radiochemical purity exceeding 97%. In cell assays, [18F]FAP-2286 showed specific uptake, high internalization fraction and low cellular efflux. Rapid tumor uptake and satisfactory tumor retention was observed on micro-PET imaging and cancer patients. Meanwhile, the clinical research demonstrated that [18F]FAP-2286 may represent an alternative for low glucose-metabolism malignant tumors PET imaging such as gastric cancers. Conclusion: [18F]FAP-2286 showed superior imaging quality including rapid and high target uptake and satisfactory retention in both tumor-bearing mice and cancer patients. It may emerge as a promising candidate for early or delayed phase imaging and 2-[18F]FDG non-avid cancers PET scan. [ABSTRACT FROM AUTHOR]

Purpose: This paper discusses the optimization of pharmacokinetic modelling and alternate simplified quantification method for [18F]AlF-P16-093, a novel tracer for in vivo imaging of prostate cancer. Methods: Dynamic PET/CT scans were conducted on eight primary prostate cancer patients, followed by a whole-body scan at 60 min post-injection. Time-activity curves (TACs) were obtained by drawing volumes of interest for primary prostatic and metastatic lesions. Optimal kinetic modelling involved evaluating three compartmental models (1T2K, 2T3K, and 2T4K) accounting for fractional blood volume (Vb). The simplified quantification method was then determined based on the correlation between the static uptake measure and total distribution volume (Vt) obtained from the optimal pharmacokinetic analysis. Results: In total, 17 intraprostatic lesions, 10 lymph nodes, and 36 osseous metastases were evaluated. Visually, the contrast of the tumor increased and showed the steepest incline within the first few minutes, whereas background activity decreased over time. Full pharmacokinetic analysis revealed that a reversible two-compartmental (2T4K) model is the preferred kinetic model for the given tracer. The kinetic parameters K1, k3, Vb, and Vt were all significantly higher in lesions when compared with normal tissue (P < 0.01). Several simplified protocols were tested for approximating comprehensive dynamic quantification in tumors, with image-based SURmean (the ratio of tumor SUVmean to blood SUVmean) within the 28–34 min window found to be sufficient for approximating the total distribution Vt values (R2 = 0.949, P < 0.01). Both Vt and SURmean correlated significantly with the total serum prostate-specific antigen (tPSA) levels (P < 0.01). Conclusions: This study introduced an optimized pharmacokinetic modelling approach and a simplified acquisition method for [18F]AlF-P16-093, a novel PSMA-targeted radioligand, highlighting the feasibility of utilizing one static PET imaging (between 30 and 60 min) for the diagnosis of prostate cancer. Note that the image-derived input function in this study may not reflect the true corrected plasma input function, therefore the interpretation of the associated kinetic parameter estimates should be done with caution. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the prognostic performance of [68Ga]Pentixafor PET/CT at baseline for staging of patients with newly diagnosed multiple myeloma (MM) and to compare it with [18F]FDG PET/CT and the Revised-International Staging System (R-ISS). Methods: Patients who underwent [68Ga]Pentixafor and [18F]FDG PET/CT imaging were retrospectively included. Patient staging was performed according to the Durie-Salmon PLUS staging system based on [68Ga]Pentixafor PET/CT and [18F]FDG PET/CT images, and the R-ISS. Progression-free survival (PFS) at patient follow-up was estimated using the Kaplan–Meier estimator and compared using the log-rank test. Area under the receiver operating characteristic curve (AUC) was calculated to assess predictive performance. Results: Fifty-five MM patients were evaluated. Compared with [18F]FDG PET, [68Ga]Pentixafor PET detected 25 patients as the same stage, while 26 patients were upstaged and 4 patients were downstaged (P = 0.001). After considering the low-dose CT data, there was no statistically significant difference in the number of patients classified in each stage using [68Ga]Pentixafor PET/CT and [18F]FDG PET/CT (P = 0.091). [68Ga]Pentixafor PET/CT-based staging discriminated PFS outcomes in patients with different disease stages (stage I vs. stage II, stage I vs. stage III, and stage II vs. stage III; all P < 0.05), whereas for [18F]FDG PET/CT, there was only a difference in median PFS between stage I and III (P = 0.021). When staged by R-ISS, the median PFS for stage III was significantly lower than that for stage I and II (P = 0.008 and 0.035, respectively). When predicting 2-year PFS based on staging, the AUC of [68Ga]Pentixafor PET/CT was significantly higher than that of [68Ga]Pentixafor PET (0.923 vs. 0.821, P = 0.002), [18F]FDG PET (0.923 vs. 0.752 P = 0.002), and R-ISS (0.923 vs. 0.776, P = 0.005). Conclusions: [68Ga]Pentixafor PET/CT-based staging possesses substantial potential to predict disease progression in newly diagnosed MM patients. [ABSTRACT FROM AUTHOR]

Purpose: Total metabolic tumor volume (TMTV) segmentation has significant value enabling quantitative imaging biomarkers for lymphoma management. In this work, we tackle the challenging task of automated tumor delineation in lymphoma from PET/CT scans using a cascaded approach. Methods: Our study included 1418 2-[18F]FDG PET/CT scans from four different centers. The dataset was divided into 900 scans for development/validation/testing phases and 518 for multi-center external testing. The former consisted of 450 lymphoma, lung cancer, and melanoma scans, along with 450 negative scans, while the latter consisted of lymphoma patients from different centers with diffuse large B cell, primary mediastinal large B cell, and classic Hodgkin lymphoma cases. Our approach involves resampling PET/CT images into different voxel sizes in the first step, followed by training multi-resolution 3D U-Nets on each resampled dataset using a fivefold cross-validation scheme. The models trained on different data splits were ensemble. After applying soft voting to the predicted masks, in the second step, we input the probability-averaged predictions, along with the input imaging data, into another 3D U-Net. Models were trained with semi-supervised loss. We additionally considered the effectiveness of using test time augmentation (TTA) to improve the segmentation performance after training. In addition to quantitative analysis including Dice score (DSC) and TMTV comparisons, the qualitative evaluation was also conducted by nuclear medicine physicians. Results: Our cascaded soft-voting guided approach resulted in performance with an average DSC of 0.68 ± 0.12 for the internal test data from developmental dataset, and an average DSC of 0.66 ± 0.18 on the multi-site external data (n = 518), significantly outperforming (p < 0.001) state-of-the-art (SOTA) approaches including nnU-Net and SWIN UNETR. While TTA yielded enhanced performance gains for some of the comparator methods, its impact on our cascaded approach was found to be negligible (DSC: 0.66 ± 0.16). Our approach reliably quantified TMTV, with a correlation of 0.89 with the ground truth (p < 0.001). Furthermore, in terms of visual assessment, concordance between quantitative evaluations and clinician feedback was observed in the majority of cases. The average relative error (ARE) and the absolute error (AE) in TMTV prediction on external multi-centric dataset were ARE = 0.43 ± 0.54 and AE = 157.32 ± 378.12 (mL) for all the external test data (n = 518), and ARE = 0.30 ± 0.22 and AE = 82.05 ± 99.78 (mL) when the 10% outliers (n = 53) were excluded. Conclusion: TMTV-Net demonstrates strong performance and generalizability in TMTV segmentation across multi-site external datasets, encompassing various lymphoma subtypes. A negligible reduction of 2% in overall performance during testing on external data highlights robust model generalizability across different centers and cancer types, likely attributable to its training with resampled inputs. Our model is publicly available, allowing easy multi-site evaluation and generalizability analysis on datasets from different institutions. [ABSTRACT FROM AUTHOR]

Aim: In addition to significant improvements in sensitivity and image quality, the recent introduction of long axial field-of-view (LAFOV) PET/CT scanners has enabled dynamic whole-body imaging for the first time. We aim herein to determine an appropriate acquisition time range for static low-dose [18F]PSMA-1007 PET imaging and to investigate the whole-body pharmacokinetics of [18F]PSMA-1007 by dynamic PET with the LAFOV Biograph Vision Quadra PET/CT in a group of prostate cancer patients. Methodology: In total, 38 prostate cancer patients were enrolled in the analysis for staging or re-staging purposes. Thirty-four patients underwent dynamic whole-body PET/CT (60 min) followed by static whole-body PET/CT and four patients underwent static whole-body PET/CT only. The activity applied was 2 MBq/kg [18F]PSMA-1007. The static PET images of 10-min duration (PET-10) were reconstructed and further split into 8-min (PET-8), 6-min (PET-6), 5-min (PET-5), 4-min (PET-4), and 2-min (PET-2) duration groups. Comparisons were made between the different reconstructed scan times in terms of lesion detection rate and image quality based on SUV calculations of tumor lesions and the spleen, which served as background. Analysis of the dynamic PET/CT data was based on a two-tissue compartment model using an image-derived input function obtained from the descending aorta. Results: Analysis of lesion detection rate showed no significant differences when reducing PET acquisitions from 10 up to 5 min. In particular, a total of 169 lesions were counted with PET-10, and the corresponding lesion detection rates (95% CI for the 90% quantile of the differences in tumor lesions) for shorter acquisitions were 100% (169/169) for PET-8 (95% CI: 0–0), 98.8% (167/169) for PET-6 (95% CI: 0–1), 95.9% (162/169) for PET-5 (95% CI: 0–3), 91.7% (155/169) for PET-4 (95% CI: 1–2), and 85.2% (144/169) for PET-2 (95% CI: 1–6). With the exception of PET-2, the differences observed between PET-10 and the other shorter acquisition protocols would have no impact on any patient in terms of clinical management. Objective evaluation of PET/CT image quality showed no significant decrease in tumor-to-background ratio (TBR) with shorter acquisition times, despite a gradual decrease in signal-to-noise ratio (SNR) in the spleen. Whole-body quantitative [18F]PSMA-1007 pharmacokinetic analysis acquired with full dynamic PET scanning was feasible in all patients. Two-tissue compartment modeling revealed significantly higher values for the parameter k3 in tumor lesions and parotid gland compared to liver and spleen, reflecting a higher specific tracer binding to the PSMA molecule and internalization rate in these tissues, a finding also supported by the respective time-activity curves. Furthermore, correlation analysis demonstrated a significantly strong positive correlation (r = 0.72) between SUV and k3 in tumor lesions. Conclusions: In prostate cancer, low-dose (2 MBq/kg) [18F]PSMA-1007 LAFOV PET/CT can reduce static scan time by 50% without significantly compromising lesion detection rate and objective image quality. In addition, dynamic PET can elucidate molecular pathways related to the physiology of [18F]PSMA-1007 in both tumor lesions and normal organs at the whole-body level. These findings unfold many of the potentials of the new LAFOV PET/CT technology in the field of PSMA-based diagnosis and theranostics of prostate cancer. [ABSTRACT FROM AUTHOR]

In men with prostate-specific membrane antigen–defined, oligorecurrent M1a–b prostate cancer, short-course androgen annihilation therapy and metastasis-directed stereotactic body radiotherapy achieved a substantial disease-free interval following testosterone recovery. This regimen was well tolerated, and 90% of patients completed therapy with androgen deprivation therapy and at least one androgen receptor pathway inhibitor. Nearly all men with metastatic hormone-sensitive prostate cancer treated with intermittent androgen deprivation therapy (ADT) experience recurrence within 6 mo of testosterone recovery. We conducted a single-arm phase 2 trial to evaluate whether addition of dual androgen receptor pathway inhibitors (ARPIs) and metastasis-directed stereotactic body radiotherapy (SBRT) to intermittent ADT improves recurrence rates for men with between one and five nonvisceral, extrapelvic metastases on prostate-specific membrane antigen positron emission tomography/computed tomography after prior radical prostatectomy. Patients received 6 mo of androgen annihilation therapy (AAT; leuprolide, abiraterone acetate plus prednisone, and apalutamide) and metastasis-directed SBRT. The primary endpoint was the percentage of patients with prostate-specific antigen (PSA) <0.05 ng/ml 6 mo after testosterone recovery (≥150 ng/dl), with the study powered to detect an improvement from 1% to 12%. We enrolled 28 men between March 2021 and June 2022. Median follow-up was 20 mo (interquartile range 16–22). Twenty-six patients (93%) completed SBRT with 6 mo of hormone therapy, of whom six discontinued at least one ARPI; two patients withdrew prematurely. At 6 mo after testosterone recovery, PSA was maintained at <0.05 ng/ml in 13/26 patients (50%, 95% confidence interval 32–67%). Rates of grade 2 and 3 AAT toxicity were 21% and 21%. The results confirm that addition of metastasis-directed SBRT to highly potent systemic therapy can maintain low PSA after testosterone recovery, although further studies are needed to clarify the optimal systemic therapy regimen. We tested a combination of intensified hormone therapy (called androgen annihilation therapy) and radiotherapy targeted at metastases in men with recurrence of metastatic prostate cancer. We found that half of patients were recurrence-free 6 months after their testosterone level recovered, and that less than a quarter of patients experienced a severe drug-related side effect. Overall, this appears to be an effective therapy with acceptable side effects. This trial is registered on ClinicalTrials.gov as NCT03902951. [ABSTRACT FROM AUTHOR]

Use of prostate-specific membrane antigen positron emission tomography to determine disease extent provides a novel method for risk stratification for patients with nonmetastatic castration-resistant prostate cancer and may contribute to future risk-adapted treatment algorithms. Previously, we demonstrated that prostate-specific membrane antigen positron emission tomography (PSMA-PET) revealed distant metastases in 109/200 patients (39% distant nodes, 24% bone, and 6% visceral organ) with nonmetastatic castration-resistant prostate cancer (nmCRPC) and high-risk features (International Society of Urological Pathology score ≥4 and/or prostate-specific antigen doubling time ≤10 mo) without metastases by conventional imaging. However, the impact of disease extent determined by PSMA-PET on patient outcomes is unknown. We followed these 200 patients for a median of 43 mo after PSMA-PET and retrospectively assessed the association between patient characteristics, PSMA-PET findings, treatment management, and outcomes using a Kaplan-Meier model and Cox multivariable regressions. Among assessed disease characteristics, polymetastatic disease (five or more distant lesions on PET) was independently associated with shorter overall survival (OS; median 61 mo vs not reached; hazard ratio [95% confidence interval], 1.81 [1.00–3.27]; p = 0.050) and time to new metastases (median 38 vs 60 mo; 1.80 [1.10–2.96]; p = 0.019), and initial pN1 status with shorter OS (55 mo vs not reached; 1.94 [1.12–3.37]; p = 0.019). Following PSMA-PET, locoregional salvage therapies were used most commonly in no/local disease (58%), and androgen receptor signaling inhibitors were used in distant metastatic disease (51%). PSMA-PET provides additional risk stratification for patients with nmCRPC. Polymetastatic disease (five or more distant lesions) is associated with worse outcomes. A novel sensitive imaging technology, called prostate-specific membrane antigen positron emission tomography (PSMA-PET), allows doctors to detect the spread of prostate cancer, known as distant metastases, earlier and more accurately than in the past. In our study, PSMA-PET detected none to many metastases in patients who were considered free of distant metastasis by conventional imaging. These findings predicted outcomes and were used to select appropriate treatment. [ABSTRACT FROM AUTHOR]

Epidemiological studies show that modifiable risk factors account for approximately 40% of the population variability in risk of developing dementia, including sporadic Alzheimer's disease (AD). Recent findings suggest that these factors may also modify disease trajectories of people with autosomal-dominant AD. With positron emission tomography imaging, it is now possible to study the disease many years before its clinical onset. Such studies can provide key knowledge regarding pathways for either the prevention of pathology or the postponement of its clinical expression. The former "resistance pathway" suggests that modifiable risk factors could affect amyloid and tau burden decades before the appearance of cognitive impairment. Alternatively, the resilience pathway suggests that modifiable risk factors may mitigate the symptomatic expression of AD pathology on cognition. These pathways are not mutually exclusive and may appear at different disease stages. Here, in a narrative review, we present neuroimaging evidence that supports both pathways in sporadic AD and autosomal-dominant AD. We then propose mechanisms for their protective effect. Among possible mechanisms, we examine neural and vascular mechanisms for the resistance pathway. We also describe brain maintenance and functional compensation as bases for the resilience pathway. Improved mechanistic understanding of both pathways may suggest new interventions. [ABSTRACT FROM AUTHOR]

Background: Surgical skills acquisition is under continuous development due to the emergence of new technologies, and there is a need for assessment tools to develop along with these. A range of neuroimaging modalities has been used to map the functional activation of brain networks while surgeons acquire novel surgical skills. These have been proposed as a method to provide a deeper understanding of surgical expertise and offer new possibilities for the personalized training of future surgeons. With studies differing in modalities, outcomes, and surgical skills there is a need for a systematic review of the evidence. This systematic review aims to summarize the current knowledge on the topic and evaluate the potential use of neuroimaging in surgical education. Methods: We conducted a systematic review of neuroimaging studies that mapped functional brain activation while surgeons with different levels of expertise learned and performed technical and non-technical surgical tasks. We included all studies published before July 1st, 2023, in MEDLINE, EMBASE and WEB OF SCIENCE. Results: 38 task-based brain mapping studies were identified, consisting of randomized controlled trials, case–control studies, and observational cohort or cross-sectional studies. The studies employed a wide range of brain mapping modalities, including electroencephalography, functional magnetic resonance imaging, positron emission tomography, and functional near-infrared spectroscopy, activating brain areas involved in the execution and sensorimotor or cognitive control of surgical skills, especially the prefrontal cortex, supplementary motor area, and primary motor area, showing significant changes between novices and experts. Conclusion: Functional neuroimaging can reveal how task-related brain activity reflects technical and non-technical surgical skills. The existing body of work highlights the potential of neuroimaging to link task-related brain activity patterns with the individual level of competency or improvement in performance after training surgical skills. More research is needed to establish its validity and usefulness as an assessment tool. [ABSTRACT FROM AUTHOR]

• Total body CT is frequently used as a diagnostic tool for FUO workup instead of FDG-PET/CT. • FDG-PET/CT is associated with higher cost and radiation exposure and lower availability. • Our results showed that total body CT achieves diagnostic rate of 40.2 % in medical patients. • In subgroup identified by elevated CRP and WBC and low hemoglobin diagnostic yield reaches 55 %. Total body computerized tomography (TBCT) is frequently used as a diagnostic tool for fever of unknown origin (FUO) workup instead of a recommended fluorodeoxyglucose positron emission tomography FDG-PET/CT. We have assessed the TBCT diagnostic yield on a large, unselected cohort of patients with FUO. We performed a single-center retrospective cohort study, examining all patients hospitalized in internal medicine between 2012 and 2019 with a documented fever and three negative blood cultures who subsequently had a total-body CT performed. After manually reviewing, we included 408 who met the criteria of FUO. We defined a positive study as a scan that led to the documented final diagnosis. A total of 164 patients (40.2 %) had a positive TBCT result. The majority of positive CT findings were of infectious etiologies (58.5 %), followed by neoplasms (22.8 %) and inflammatory disorders (14.0 %), with the chest (43.9 %) and abdomen (29.8 %) most affected. Using a logistic regression model, a positive scan results were associated with an elevated CRP (p <0.001). Decision tree analysis showed that 55 % of scans of patients with an elevated CRP (>6 mg/dL), low hemoglobin and high leucocyte count (>18000/ml) were positive. Patients without an elevated CRP had a positive scan in only 26 % of tests, and those with also an elevated albumin (>4 gr/dL) and low CRP had positive scan in only 11 % of cases. TBCT has a clinically significant yield under specific clinical scenarios in medical patients with FUO- reaching 55 % in patients with an elevated CRP and leukocyte count and low hemoglobin. It is reasonable to proceed to TTBCT when FDG-PET/CT is unavailable and in well-defined clinical situations. [ABSTRACT FROM AUTHOR]

Our main goal of this meta-analytical analysis was to evaluate the diagnostic effectiveness of prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) against multiparametric magnetic resonance imaging (mpMRI) in the context of identifying biochemical recurrence in patients with prostate cancer (PCa). A thorough search covering articles published until March 2023 was carried out across major databases such as PubMed, Embase, and Web of Science. Studies examining the direct comparison of PSMA PET/CT and mpMRI in patients with PCa suffering biochemical recurrence were included in the inclusion criteria. Using the renowned Quality Assessment of Diagnostic Performance Studies-2 technique, each study's methodological rigor was assessed. We analyzed data from six eligible studies involving 290 patients in total. The combined data showed that for PSMA PET/CT and mpMRI, respectively, the pooled overall detection rates for recurrent PCa after definitive treatment were 0.69 (95% confidence interval [CI]: 0.45–0.89) and 0.70 (95% CI: 0.44–0.91). The detection rates for local recurrence were specifically 0.52 (95% CI: 0.39–0.65) and 0.62 (95% CI: 0.31–0.89), while they were 0.50 (95% CI: 0.26–0.74) and 0.32 (95% CI: 0.18–0.48) for lymph node metastasis. Notably, there was no discernible difference between the two imaging modalities in terms of the overall detection rate (P = 0.95). The detection rates for local recurrence and lymph node metastasis did not differ statistically significantly (P = 0.55, 0.23). The performance of PSMA PET/CT and mpMRI in identifying biochemical recurrence in PCa appears to be comparable. However, the meta-analysis' findings came from research with modest sample sizes. In this context, more extensive research should be conducted in the future. • Pooled detection rates for recurrent prostate cancer (PCa): 0.69 with prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT), 0.70 with multiparametric magnetic resonance imaging (mpMRI). • PSMA PET/CT and mpMRI perform equally in detecting PCa recurrence. • This article is a head-to-head comparative meta-analysis. [ABSTRACT FROM AUTHOR]

To evaluate the diagnostic performance of 2-[18F]-fluoro-2-deoxy- d -glucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) in TA diagnosis and Takayasu arteritis (TA) activity assessment. This retrospective study included patients with TA diagnosed according to the American College of Rheumatology (ACR) criteria and undergoing 18F-FDG PET/CT imaging from October 2010 to July 2022. TA activity was assessed through 18F-FDG PET/CT (maximum standard uptake value [SUVmax], vascular SUVmax/mean standard uptake value [SUVmean] of liver (SUV ratio), and PET vascular activity score [PETVAS]) using physician global assessment (PGA) as the reference standard, and the results of these assessments were compared against the clinical activity scores (National Institutes of Health [NIH] and Indian Aortitis Disease Activity [ITAS-A] scores), acute-phase reactants (APR), and white blood cell and platelet counts. Twenty 18F-FDG PET/CT examinations from 19 patients were included in the study, nine were performed in the active phase and 11 in the inactive phase. The involved vessels showed segmental and tubular FDG uptake in the active group. The average SUVmax, SUV ratio, and PETVAS was 6.3 ± 2.7 (range 3.4–12), 4.2 ± 1.7 (range 2.1–7.5), and 22.7 ± 11.2 (range 6–39), respectively, in the active group and 1.7 ± 0.9 (0.9–3.1), 1.1 ± 0.6 (range 0.6–2.4), and 3.5 ± 5.5 (range 0–18), respectively, in the inactive group. The sensitivity, specificity of SUVmax, SUV ratio, and PETVAS for TA activity assessment were 100%, 100%; 100%, 90.9%; and 88.9, 90.9%, respectively. After ROC curve analysis, a new SUVmax cut-off was obtained. Based on the new cut-off value, SUVmax 3.3 and SUV ratio 1.9 had a more perfect assessment performance. 18F-FDG PET/CT is an alternative imaging technique for TA. • 18F-FDG PET/CT has advantages in TAK activity assessment. • Arterial SUVmax and SUV target/background ratio are important parameters for TAK activity assessment. • 18F-FDG PET/CT allows for a more accurate classification of TAK. • PET/CT can better evaluate TAK efficacy [ABSTRACT FROM AUTHOR]

Multimodal treatment approaches with neoadjuvant radiotherapy and chemotherapy followed by oncological and total mesorectal excision (TME) have significantly reduced the recurrence rate even in locally advanced rectal cancer. Nevertheless, up to 10% of patients develop a local relapse. Surgical R0 resection is the only chance of a cure in the treatment of locally recurrent rectal cancer (LRRC). Due to the altered anatomy and physiology of the true pelvis as a result of the pretreatment and operations as well as the localization and extent of the recurrence, the treatment decision is individualized and remains a challenge for the interdisciplinary team. Even locally advanced tumors with involvement of adjacent structures can be treated in designated centers using multimodal treatment concepts with potentially curative intent. [ABSTRACT FROM AUTHOR]