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Background: [18F]FDG PET denoising by SubtlePET™ using deep learning artificial intelligence (AI) was previously found to induce slight modifications in lesion and reference organs' quantification and in lesion detection. As a next step, we aimed to evaluate its clinical impact on [18F]FDG PET solid tumour treatment response assessments, while comparing "standard PET" to "AI denoised half-duration PET" ("AI PET") during follow-up. Results: 110 patients referred for baseline and follow-up standard digital [18F]FDG PET/CT were prospectively included. "Standard" EORTC and, if applicable, PERCIST response classifications by 2 readers between baseline standard PET1 and follow-up standard PET2 as a "gold standard" were compared to "mixed" classifications between standard PET1 and AI PET2 (group 1; n = 64), or between AI PET1 and standard PET2 (group 2; n = 46). Separate classifications were established using either standardized uptake values from ultra-high definition PET with or without AI denoising (simplified to "UHD") or EANM research limited v2 (EARL2)-compliant values (by Gaussian filtering in standard PET and using the same filter in AI PET). Overall, pooling both study groups, in 11/110 (10%) patients at least one EORTCUHD or EARL2 or PERCISTUHD or EARL2 mixed vs. standard classification was discordant, with 369/397 (93%) concordant classifications, unweighted Cohen's kappa = 0.86 (95% CI: 0.78–0.94). These modified mixed vs. standard classifications could have impacted management in 2% of patients. Conclusions: Although comparing similar PET images is preferable for therapy response assessment, the comparison between a standard [18F]FDG PET and an AI denoised half-duration PET is feasible and seems clinically satisfactory. [ABSTRACT FROM AUTHOR]

Introduction: Data acquisition and image reconstruction protocols affect image quality and quantification accuracy in PET imaging. We aimed to standardize and optimize image acquisition, and reconstruction parameter sets using a simultaneous quantitative and qualitative assessment framework for a lutetium oxyorthosilicate (LSO)-based PET/CT scanner. Methods: The NEMA IEC Body Phantom acquisition was performed in list mode for 10 minutes with four spheres to background ratios (SBRs). Raw PET data were reconstructed using 60 different protocols. Image quality was evaluated for standardization using contrast, CNR, and noise. Recovery coefficient (RC) measurements were performed for different common VOI definitions. Results: No significant differences were observed between RCs for various acquisition durations. The contrast to noise ratio (CNR) increased at all SBRs by expanding the acquisition duration from 60 to 600 seconds. PET scan time was reduced to 90 seconds per bed position while preserving image quality. Up to 50% improvement in CNR for the highest sub-iteration with a high level of smoothing was observed. PSF-based reconstruction produced a positive bias of RCmax in high SBRs (8 and 10) using higher sub-iterations (30 to 60) with Gaussian filters less than 6 mm FWHM. Moreover, a Sub-iteration of more than 32 with a 4-6 mm FWHM Gaussian filter provides optimized reconstruction sets. Conclusion: Our study demonstrates it would be feasible for PET image acquisition and reconstruction settings to simultaneously allow optimal lesion detection with high image quality while providing accurate quantification. [ABSTRACT FROM AUTHOR]

Introduction: Pediatric patients have an increased risk of radiation-induced malignancies due to their ongoing development and long remaining life span. Thus, optimization of PET protocols is an important task in pediatric nuclear medicine. Long axial field-of-view (LAFOV) PET/CT has shown a significant increase in sensitivity, which provides an ideal opportunity for reduction of injected tracer activity in the pediatric population. In this study we aim to evaluate the clinical performance of a 2-[18F]FDG-tracer reduction from 3 MBq/kg to 1.5 MBq/kg on the Biograph Vision Quadra LAFOV PET/CT. Materials and methods: The first 50 pediatric patients referred for clinical whole-body PET/CT with 1.5 MBq/kg 2-[18F]FDG, were included. A standard pediatric protocol was applied. Five reconstructions were created with various time, filter and iteration settings. Image noise was computed as coefficient-ofvariance (COV = SD/mean standardized-uptake-value) calculated from a spherical 20--50 mm (diameter) liver volume-of-interest. Sets of reconstructions were reviewed by one nuclear medicine physicians, who reported image lesions on a pre-defined list of sites. Paired comparison analysis was performed with significance at PB < 0.05 (Bonferroni corrected). Results: All reconstructions, except one, achieved a COVmean (0.08--0.15) equal to or lower than current clinical acceptable values (COVref ≤ 0.15). Image noise significantly improved with increasing acquisition time, lowering iterations (i) from 6i to 4i (both with five subsets) and when applying a 2 mm Gauss filter (PB < 0.001). Significant difference in lesion detection was seen from 150s to 300s and from 150s to 600s (PB = 0.006--0.007). 99% of all lesions rated as malignant could be found on the 150s reconstruction, while 100% was found on the 300s, when compared to the 600s reconstruction. Conclusion: Injected activity and scan time can be reduced to 1.5 MBq/kg 2-[18F] FDG with 5 min acquisition time on LAFOV PET/CT, while maintaining clinical performance in the pediatric population. These results can help limit radiation exposure to patients and personnel as well as shorten total scan time, which can help increase patient comfort, lessen the need for sedation and provide individually tailored scans. [ABSTRACT FROM AUTHOR]

Background: Practice effects on cognitive testing in mild cognitive impairment (MCI) and Alzheimer's disease (AD) remain understudied, especially with how they compare to biomarkers of AD. Objective: The current study sought to add to this growing literature. Methods: Cognitively intact older adults (n = 68), those with amnestic MCI (n = 52), and those with mild AD (n = 45) completed a brief battery of cognitive tests at baseline and again after one week, and they also completed a baseline amyloid PET scan, a baseline MRI, and a baseline blood draw to obtain APOE ɛ4 status. Results: The intact participants showed significantly larger baseline cognitive scores and practice effects than the other two groups on overall composite measures. Those with MCI showed significantly larger baseline scores and practice effects than AD participants on the composite. For amyloid deposition, the intact participants had significantly less tracer uptake, whereas MCI and AD participants were comparable. For total hippocampal volumes, all three groups were significantly different in the expected direction (intact > MCI > AD). For APOE ɛ4, the intact had significantly fewer copies of ɛ4 than MCI and AD. The effect sizes of the baseline cognitive scores and practice effects were comparable, and they were significantly larger than effect sizes of biomarkers in 7 of the 9 comparisons. Conclusion: Baseline cognition and short-term practice effects appear to be sensitive markers in late life cognitive disorders, as they separated groups better than commonly-used biomarkers in AD. Further development of baseline cognition and short-term practice effects as tools for clinical diagnosis, prognostic indication, and enrichment of clinical trials seems warranted. [ABSTRACT FROM AUTHOR]

Background: Pancreatic neuroendocrine tumors (P-NETs) constitute a subset of pancreatic mass lesions characterized by diverse clinical presentations. Despite their inherent malignant potential, the timely identification and treatment of these tumors are critical for achieving favorable clinical outcomes. This study aims to shed light on the heterogeneous tumor biology of P-NETs and the management strategies employed at a tertiary care center in Pakistan. Method: A retrospective study encompassing all patients with a biopsy-confirmed diagnosis of P-NETs at Shifa International Hospital between January 1st, 2016, and June 30th, 2021, was conducted. Meticulous data extraction from pathology records and thorough searches of medical records were performed to gather relevant demographic and clinical information. Results: A total of 24 patients were retrieved from our database, with 13 (54%) female patients. The mean age was 49.5 ± 16.3 years. Eight out of the 24 patients presented with abdominal pain. Most patients (14 out of 24) had lesions in the pancreatic head region. In three cases, lesions exhibited multicentricity. The mean lesion size measured 4.4 ± 2.3 cm. Three of the 24 patients displayed distant liver metastasis at the presentation time. 19 out of the 24 patients underwent surgical resections, while endoscopic ultrasound (EUS)-guided biopsy was performed in 4 out of 24 cases. EUS-guided tissue biopsy yielded accurate diagnoses in all four cases. Conclusion: Most P-NETs are non-functional, and there is an almost equal distribution between male and female patients. Solitary lesions predominate, and metastasis is uncommon at initial presentation. EUS-guided fine needle biopsy stands out as a dependable diagnostic modality for P-NETs. [ABSTRACT FROM AUTHOR]

Background: Standard measures of response such as Response Evaluation Criteria in Solid Tumors are ineffective for bone lesions, often making breast cancer patients that have bone-dominant metastases ineligible for clinical trials with potentially helpful therapies. In this study we prospectively evaluated the test-retest uptake variability of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) in a cohort of breast cancer patients with bone-dominant metastases to determine response criteria. The thresholds for 95% specificity of change versus no-change were then applied to a second cohort of breast cancer patients with bone-dominant metastases. Methods: For this study, nine patients with 38 bone lesions were imaged with 18F-FDG in the same calibrated scanner twice within 14 days. Tumor uptake was quantified by the most commonly used PET parameter, the maximum tumor voxel normalized by dose and body weight (SUVmax) and also by the mean of a 1-cc maximal uptake volume normalized by dose and lean-body-mass (SULpeak). The asymmetric repeatability coefficients with confidence intervals for SUVmax and SULpeak were used to determine the limits of 18F-FDG uptake variability. A second cohort of 28 breast cancer patients with bone-dominant metastases that had 146 metastatic bone lesions was imaged with 18F-FDG before and after standard-of-care therapy for response assessment. Results: The mean relative difference of SUVmax and SULpeak in 38 bone tumors of the first cohort were 4.3% and 6.7%. The upper and lower asymmetric limits of the repeatability coefficient were 19.4% and − 16.3% for SUVmax, and 21.2% and − 17.5% for SULpeak. 18F-FDG repeatability coefficient confidence intervals resulted in the following patient stratification using SULpeak for the second patient cohort: 11-progressive disease, 5-stable disease, 7-partial response, and 1-complete response with three inevaluable patients. The asymmetric repeatability coefficients response criteria for SULpeak changed the status of 3 patients compared to the standard Positron Emission Tomography Response Criteria in Solid Tumors of ± 30% SULpeak. Conclusion: In evaluating bone tumor response for breast cancer patients with bone-dominant metastases using 18F-FDG SUVmax, the repeatability coefficients from test-retest studies show that reductions of more than 17% and increases of more than 20% are unlikely to be due to measurement variability. Serial 18F-FDG imaging in clinical trials investigating bone lesions in these patients, such as the ECOG-ACRIN EA1183 trial, benefit from confidence limits that allow interpretation of response. [ABSTRACT FROM AUTHOR]

Objective approaches to treatment. [ABSTRACT FROM AUTHOR]

Background: A comprehensive overview of artificial intelligence (AI) for cardiovascular disease (CVD) prediction and a screening tool of AI models (AI-Ms) for independent external validation are lacking. This systematic review aims to identify, describe, and appraise AI-Ms of CVD prediction in the general and special populations and develop a new independent validation score (IVS) for AI-Ms replicability evaluation. Methods: PubMed, Web of Science, Embase, and IEEE library were searched up to July 2021. Data extraction and analysis were performed for the populations, distribution, predictors, algorithms, etc. The risk of bias was evaluated with the prediction risk of bias assessment tool (PROBAST). Subsequently, we designed IVS for model replicability evaluation with five steps in five items, including transparency of algorithms, performance of models, feasibility of reproduction, risk of reproduction, and clinical implication, respectively. The review is registered in PROSPERO (No. CRD42021271789). Results: In 20,887 screened references, 79 articles (82.5% in 2017–2021) were included, which contained 114 datasets (67 in Europe and North America, but 0 in Africa). We identified 486 AI-Ms, of which the majority were in development (n = 380), but none of them had undergone independent external validation. A total of 66 idiographic algorithms were found; however, 36.4% were used only once and only 39.4% over three times. A large number of different predictors (range 5–52,000, median 21) and large-span sample size (range 80–3,660,000, median 4466) were observed. All models were at high risk of bias according to PROBAST, primarily due to the incorrect use of statistical methods. IVS analysis confirmed only 10 models as "recommended"; however, 281 and 187 were "not recommended" and "warning," respectively. Conclusion: AI has led the digital revolution in the field of CVD prediction, but is still in the early stage of development as the defects of research design, report, and evaluation systems. The IVS we developed may contribute to independent external validation and the development of this field. [ABSTRACT FROM AUTHOR]

Circulating tumor DNA (ctDNA), which circulates in the blood after being shed from cancer cells in the body, has recently gained attention as an excellent tumor marker. The purpose of this study was to evaluate whether ct human papillomavirus (HPV) 16 DNA (ctHPV16DNA) levels were associated with quantitative PET parameters in patients with HPV-positive head and neck (HN) squamous cell carcinoma (SCC). Fifty patients with oropharyngeal SCC (OPSCC) and 5 with SCC of unknown primary (SCCUP) before treatment were included. They all underwent blood sampling to test ctHPV16DNA levels and FDG PET-CT examinations. Quantitative PET parameters included SUVmax, metabolic tumor volume (MTV), MTV of whole-body lesions (wbMTV), and 56 texture features. ctHPV16DNA levels were compared to texture features of primary tumors in OPSCC patients (Group A) or the largest primary or metastatic lymph node lesions in OPSCC and SCCUP patients (Group B) and to other PET parameters. Spearman rank correlation test and multiple regression analysis were used to confirm the associations between ctHPV16DNA levels and PET parameters. ctHPV16DNA levels moderately correlated with wbMTV, but not with SUVmax or MTV in Groups A and B. ctHPV16DNA levels exhibited a weak negative correlation with low gray-level zone emphasis in Groups A and B. Multiple regression analysis revealed that wbMTV and high gray-level zone emphasis were the significant factors for ctHPV16DNA levels in Group B. These results were not observed in Group A. This study demonstrated that ctHPV16DNA levels correlated with the whole-body tumor burden and tumor heterogeneity visualized on FDG PET-CT in patients with HPV-positive HNSCC. [ABSTRACT FROM AUTHOR]

Introduction: Functional informaton is introduced as the mechanism to adapt cancer therapies uniquely to individual patients based on changes defined by qualified tumor biomarkers. Methods: To demonstrate the methodology, a tumor volume biomarker model, characterized by a tumor volume reduction rate coefficient, is used to adapt a tumor cell survival bioresponse radiotherapy model in terms of therapeutic radiation dose. Tumor volume, acquired from imaging data, serves as a surrogate measurement for tumor cell death, but the biomarker model derived from this data cannot be used to calculate the radiation dose absorbed by the target tumor. However, functional information does provide a mathematical connection between the tumor volume biomarker model and the tumor cell survival bioresponse model by quantifying both data sets in the units of information, thus creating an analytic conduit from bioresponse to biomarker. Results: The information guided process for individualized dose adaptations using information values acquired from the tumor cell survival bioresponse model and the tumor volume biomarker model are presented in detailed form by flowchart and tabular data. Clinical data are used to generate a presentation that assists investigator application of the information guided methodology to adaptive cancer therapy research. Conclusions: Information guided adaptation of bioresponse using surrogate data is extensible across multiple research fields because functional information mathematically connects disparate bioresponse and biomarker data sets. Thus, functional information offers adaptive cancer therapy by mathematically connecting immunotherapy, chemotherapy, and radiotherapy cancer treatment processes to implement individualized treatment plans. [ABSTRACT FROM AUTHOR]

Background: Chronic postsurgical pain (CPP) markedly impairs patients' quality of life. Research has shown that chronic stress may extend incisional nociception in male mice. Dopaminergic (DAergic) neurons in the ventral tegmental area (VTA) are integral to stress-related mental disorders (including major depressive disorder, anxiety disorders, and PTSD) and pain. However, the impact of chronic social defeat stress (CSDS) on mesolimbic dopamine (DA) transmission in the development of CPP is yet to be established. It remains uncertain whether the dopamine signals in the rostral anterior cingulate cortex (rACC), which regulate pain, derive from the VTA. This study aims to explore the role of VTA-rACC dopaminergic circuits in a mouse model of CPP induced by CSDS. Methods: We conducted CSDS on C57BL/6 J wild-type male mice (n = 12–16 mice/group) and DAT-cre male mice (n = 10–12 mice/group). After 10 days of CSDS, a left posterior plantar incision was made to establish a mouse model of CPP. Paw withdrawal thresholds (PWTs) were evaluated using Von-Frey fibre stimulation. The open field test (OFT) and elevated plus maze test (EPM) were used to assess pain-related negative emotions. We used immunofluorescence staining and Western Blot to analyse D1, D2, c-Fos, and TH expression. DAergic fibre projections in the VTA-rACC neural pathway were traced using retrograde tracing and immunofluorescence staining. Optogenetics and Chemogenetics were employed to manipulate DAergic neurons in the VTA and their axons in the rACC. Results: The ipsilateral PWTs in male C57BL/6 J mice significantly decreased after surgery, returning to baseline after seven days. Conversely, in CSDS mice, ipsilateral PWTs remained reduced for at least 30 days post-incision. A significant reduction in TH-positive neurons expressing c-Fos in the VTA of CPP mice was observed 15 days post-incision. Activating DAergic neurons significantly improved ipsilateral PWTs and locomotor performance in the OFT and EPM in CPP mice post-incision. Additionally, D1 expression in the rACC was found to decrease in CPP mice, and this reduction counteracted the increase in PWTs caused by activating DAergic neuron axon terminals in the rACC. Conclusion: CSDS results in chronicity of postsurgical nociception and anxiety-like negative emotions, with alterations in DA transmission playing a role in CPP. Specific activation of DAergic neurons mitigates nociceptive responses and anxiety-like bahaviors, possibly mediated by D1 receptors in the rACC. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The standardized uptake value ratio (SUVR) is used to measure amyloid beta–positron emission tomography (Aβ‐PET) uptake in the brainDifferences in PET scanner technologies and image reconstruction techniques can lead to variability in PET images across scanners. This poses a challenge for Aβ‐PET studies conducted in multiple centers. The aim of harmonization is to achieve consistent Aβ‐PET measurements across different scanners. In this study, we propose an Aβ‐PET harmonization method of matching spatial resolution, as measured via a barrel phantom, across PET scanners. Our approach was validated using paired subject data, for which patients were imaged on multiple scanners. METHODS: In this study, three different PET scanners were evaluated: the Siemens Biograph Vision 600, Siemens Biograph molecular computed tomography (mCT), and Philips Gemini TF64. A total of five, eight, and five subjects were each scanned twice with [18F]‐NAV4694 across Vision‐mCT, mCT‐Philips, and Vision‐Philips scanner pairs. The Vision and mCT scans were reconstructed using various iterations, subsets, and post‐reconstruction Gaussian smoothing, whereas only one reconstruction configuration was used for the Philips scans. The full‐width at half‐maximum (FWHM) of each reconstruction configuration was calculated using [18F]‐filled barrel phantom scans with the Society of Nuclear Medicine and Molecular Imaging (SNMMI) phantom analysis toolkit. Regional SUVRs were calculated from 72 brain regions using the automated anatomical labelling atlas 3 (AAL3) atlas for each subject and reconstruction configuration. Statistical similarity between SUVRs was assessed using paired (within subject) t‐tests for each pair of reconstructions across scanners; the higher the p‐value, the greater the similarity between the SUVRs. RESULTS: Vision‐mCT harmonization: Vision reconstruction with FWHM = 4.10 mm and mCT reconstruction with FWHM = 4.30 mm gave the maximal statistical similarity (maximum p‐value) between regional SUVRs. Philips‐mCT harmonization: The FWHM of the Philips reconstruction was 8.2 mm and the mCT reconstruction with the FWHM of 9.35 mm, which gave the maximal statistical similarity between regional SUVRs. Philips–Vision harmonization: The Vision reconstruction with an FWHM of 9.1 mm gave the maximal statistical similarity between regional SUVRs when compared with the Philips reconstruction of 8.2 mm and were selected as the harmonized for each scanner pair. CONCLUSION: Based on data obtained from three sets of participants, each scanned on a pair of PET scanners, it has been verified that using reconstruction configurations that produce matched‐barrel, phantom spatial resolutions results in maximally harmonized Aβ‐PET quantitation between scanner pairs. This finding is encouraging for the use of PET scanners in multi‐center trials or updates during longitudinal studies. Highlights: Question: Does the process of matching the barrel phantom‐derived spatial resolution between scanners harmonize amyloid beta–standardized uptake value ratio (Aβ‐SUVR) quantitation?Pertinent findings: It has been validated that reconstruction pairs with matched barrel phantom‐derived spatial resolution maximize the similarity between subjects paired Aβ‐PET (positron emission tomography) SUVR values recorded on two scanners.Implications for patient care: Harmonization between scanners in multi‐center trials and PET camera updates in longitudinal studies can be achieved using a simple and efficient phantom measurement procedure, beneficial for the validity of Aβ‐PET quantitation measurements. [ABSTRACT FROM AUTHOR]

PET/CT and radioisotope therapy are diagnostic and therapeutic arms of Nuclear Medicine, respectively. With the emergence of better technology, PET/CT has become an accessible modality. Diagnostic tracers exploring diseasespecific targets has led the clinicians to look beyond FDG PET. Moreover, with the emergence of theranostic pairs of radiopharmaceuticals, radioisotope therapy is gradually making it's way into treatment algorithm of common cancers in India. We therefore would like to discuss in detail the updates in PET/CT imaging and radionuclide therapy and generate a consensus-driven evidence based document which would guide the practitioners of Oncology. [ABSTRACT FROM AUTHOR]

Background: Modern PET reconstruction algorithms incorporate point-spread-function (PSF) correction to mitigate partial volume effect. However, PSF correction can introduce edge artifacts that lead to quantification errors. Consequently, current international guidelines advise against using PSF correction in brain PET reconstruction., Purpose: We aimed to investigate PSF-induced quantification errors in recent digital PET systems and identify conditions that mitigate them. This study utilized brain PET imaging with alginate-based realistic phantoms, simulating lesion-to-background activity ratios of 10:1 and 2:1, with eleven reconstruction parameter sets., Methods: Phantoms were prepared using a commercial anthropomorphic head phantom and two homemade inserts. Each insert contained a homogeneous 18 F-FDG alginate background with hot spheres of varying diameter (3, 4, 6, 8, 10, 12, and 15 mm). PET imaging was conducted on a digital PET-CT system Biograph Vision 600 (Siemens), with a 10 min scan duration. Imaging was performed with and without PSF correction, with 2, 4, 6, 12, 18, or 24 iterations in reconstruction, and with or without additional Gaussian postfiltering. We assessed the recovery coefficient (RC), contrast recovery coefficient (CRC), variability, and CRC-to-variability ratios for each sphere size and reconstruction parameter set., Results: PSF-corrected images of the 10:1 spheres exhibited a nonmonotonic CRC-to-sphere diameter relationship due to edge artifacts overshoot in the 10 mm-diameter sphere. In contrast, PSF images of the 2:1 spheres showed a monotonically increasing relationship. Non-PSF images of both phantoms showed an expected monotonically increasing CRC-to-sphere diameter relationship but with lower CRC values compared to PSF images. The nonmonotonic relationship observed with 10:1 spheres was mitigated by applying a 3-mm FWHM Gaussian postfiltering. For both phantoms, reconstructions with 6 iterations, PSF correction, and additional 3-mm FWHM Gaussian postfiltering demonstrated the highest CRC-to-variability ratios., Conclusions: Our findings indicate that Gaussian postfiltering suppresses PSF artifacts. This parameter set corrected the nonmonotonic CRC-to-sphere diameter relationship and improved the CRC-to-variability ratio compared to non-PSF reconstructions. Therefore, to enhance lesion detectability without compromising quantification accuracy, PSF correction coupled with Gaussian postfiltering should be used in brain PET., (© 2024 American Association of Physicists in Medicine.)

Although peptide radionuclide therapy (PRRT) using a somatostatin analog (SSA) radiolabeled with a beta- emitter: [ 177 Lu]Lu-DOTATATE has shown a good clinical efficacy in neuroendocrine tumors (NETs), most of the patients only achieved tumoral stabilization and rare but severe long-term hematological toxicities have been reported. One of the promising options to improve PRRT is targeted alpha therapy. It is therefore essential to propose animal models that can mimic systemic spread disease, especially microscopic disease such as early stage of NET liver metastases to explore targeted alpha therapy. Herein, we report the evaluation of efficacy and toxicity of [ 225 Ac]Ac-DOTATOC in an original preclinical murine model simulating the development of well-characterized liver metastases of pancreatic NETs with SSTR overexpression., Methods: A mouse model of liver metastases of pancreatic NETs was developed by intraportal injection of AR42J cells and explored using [ 68  Ga]Ga-DOTATOC and [ 18 F]F-FDG PET/MRI. Biodistribution study and radiation dosimetry of [ 225 Ac]Ac-DOTATOC were determined in subcutaneous tumor-bearing NMRI-nude mice. Efficacy and toxicity were determined by intravenous injection of increasing activities of [ 225 Ac]Ac-DOTATOC 10 days after intraportal graft., Results: Liver tumors showed a high uptake of [ 68  Ga]Ga-DOTATOC and no uptake of [ 18 F]F-FDG confirming the well-differentiated phenotype. All groups treated with [ 225 Ac]Ac-DOTATOC showed a significant increase in overall survival compared with DOTATOC-treated mice, especially those treated with the highest activities: 53 days with 240 kBq (p = 0.0001), and 58 days with 2 × 120 kBq (p < 0.0001) vs 28 days with non-radiolabeled DOTATOC. On blood tests, a transient and moderate decreased in white blood cells count after treatment and no severe hepatic or renal toxicity were observed after treatment which was consistent with pathological and radiation dosimetry findings., Conclusion: [ 225 Ac]Ac-DOTATOC exhibit a favorable efficacy and toxicity profile in a mouse model of liver micrometastatic pancreatic NET., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Point-spread-function (PSF) correction is not recommended for amyloid PET images due to Gibbs artifacts. Q.Clear™, a Bayesian Penalized Likelihood (BPL) reconstruction method without incorporating PSF correction reduces these artifacts but degrades image contrast by our previous findings. The present study aimed to recover lost contrast by optimizing reconstruction parameters in time-of-flight (TOF) BPL reconstruction of amyloid PET images without PSF correction. We selected candidate conditions based on a phantom study and then determined which were optimal in a clinical study. Phantom images were reconstructed under conditions of 1‒9 iterations, β 300-1000 and γ factors from 2 to 10 in TOF-BPL without PSF correction. We evaluated the %contrast and the coefficients of variation (CV, %). Standardized uptake value ratios (SUVr) and Centiloid scales (CL) were calculated from PET images acquired from 71 participants after an [ 18 F]flutemetamol injection. Both %contrast and CV were independent of iterations, whereas a trade-off was found between γ factors and β. We selected a γ factors of 5 without PSF correction (iterations, 1; β, 500) and of 10 without PSF correction (iterations, 1; β, 800) as candidates for clinical investigation. The SUVr and CL remained stable across various conditions, and CL scales effectively discriminated amyloid PET using measured values. The optimal reconstruction parameters of TOF-BPL for [ 18 F]flutemetamol PET images were γ factor 10, iterations 1 and β 800, without PSF correction., (© 2024. Australasian College of Physical Scientists and Engineers in Medicine.)

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-[ 18 F]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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Advancements in molecular imaging and drug targeting have created a renaissance in the development of radiopharmaceuticals for therapy and theranostics. While some radiopharmaceuticals, such as Na[ 131 I]I, have been used clinically for decades, new agents are being approved using small-molecules, peptides, and antibodies for targeting. As these agents are being developed, the need to understand dosimetry and biologic effects of the systemically delivered radiotherapy becomes more important, particularly as highly potent radiopharmaceuticals using targeted alpha therapy become clinically utilized. As the processes being targeted become more complex, and the radiobiology of different particulate radiation becomes more diverse, models that better recapitulate human cancer and geometry are necessary. Companion animals develop many of the same types of cancer, carrying many of the same genetic drivers as those seen in people, and the scale and geometry of tumours in dogs more closely mimics those in humans than murine tumour models. Key translational challenges in oncology, such as alterations in tumour microenvironment, hypoxia, heterogeneity, and geometry are addressed by companion animal models. This review paper will provide background on radiopharmaceutical targeting techniques, review the use of radiopharmaceuticals in companion animal oncology, and explore the translational value of treating these patients in terms of dosimetry, treatment outcomes, and normal tissue complication rates., (© 2024 John Wiley & Sons Ltd.)

Purpose: We aimed to determine the test-retest repeatability of quantitative metrics based on the Patlak slope (PS) versus the standardized uptake value (SUV) among lesions and normal organs on oncologic [ 18 F]FDG-PET/CT., Procedures: This prospective, single-center study enrolled adults undergoing standard-of-care oncologic [ 18 F]FDG-PET/CTs. Early (35-50 min post-injection) and late (75-90 min post-injection) SUV and PS images were reconstructed from dynamic whole-body PET data. Repeat imaging occurred within 7 days. Relevant quantitative metrics were extracted from lesions and normal organs. Repeatability was assessed via mean test-retest percent changes [T-RT %Δ], within-subject coefficients of variation (wCVs), and intra-class correlation coefficients (ICCs)., Results: Nine subjects (mean age, 61.7 ± 6.2 years; 6 females) completed the test-retest protocol. Four subjects collectively had 17 [ 18 F]FDG-avid lesions. Lesion wCVs were higher (i.e., worse repeatability) for PS-early-max (16.2%) and PS-early-peak (15.6%) than for SUV-early-max (8.9%) and SUV-early-peak (8.1%), with similar early metric ICCs (0.95-0.98). Lesion wCVs were similar for PS-late-max (8.5%) and PS-late-peak (6.4%) relative to SUV-late-max (9.7%) and SUV-late-peak (7.2%), with similar late metric ICCs (0.93-0.98). There was a significant bias toward higher retest SUV and PS values in the lesion analysis (T-RT %Δ [95% CI]: SUV-late-max, 10.0% [2.6%, 17.0%]; PS-late-max, 20.4% [14.3%, 26.4%]) but not in the normal organ analysis., Conclusions: Among [ 18 F]FDG-avid lesions, the repeatability of PS-based metrics is similar to equivalent SUV-based metrics at late post-injection time points, indicating that PS-based metrics may be suitable for tracking response to oncologic therapies. However, further validation is required in light of our study's limitations, including small sample size and bias toward higher retest values for some metrics., (© 2024. The Author(s), under exclusive licence to World Molecular Imaging Society.)

Background: Studying biomarkers in children with temporomandibular disorders (TMD) such as epinephrine, norepinephrine, and dopamine may reveal factors like screen time or sleep loss that affect these biomarkers and predict TMD-related pain, offering new research opportunities., Aim: To determine the association between stress and catecholamines with myofascial pain and headache related to TMD in children., Design: Sixty-six 9- to 11-year-old children assisting at the clinics of Pediatric Dentistry of Universidad CES participated in the study. Myofascial pain and headache attributed to TMD were determined according to the Diagnostic Criteria for TMD (DC/TMD) Axis I. Stress was evaluated with the Perceived Stress Scale-Children (PSS-C), and a 24-h urine sample was analyzed using liquid chromatography to assay catecholamines. Single and multiple regression analyses were performed., Results: Children with a mean age of 10.3 years participated in the study. The mean score of stress was 29 ± 4. Perceived stress, dopamine, epinephrine, and norepinephrine were statistically significant predictors of myofascial pain and headache attributed to TMD in the single- and multiple variable logistic regression analyses., Conclusion: Stressful states and its biological biomarkers increase the probability of developing myofascial pain and headache attributed to TMD in children., (© 2024 BSPD, IAPD and John Wiley & Sons Ltd.)

Purpose: Currently, the most used peptide receptor radionuclide therapy (PRRT) regimen for neuroendocrine tumors comprises 4 treatment cycles, and there is not enough large-scale data to support the safety of more individualized extended PRRT. This study aims to evaluate the therapeutic effectiveness and potential nephrotoxicity related to PRRT using more than four treatment cycles., Methods: In this retrospective analysis, we included patients who had received at least four PRRT cycles and had available follow-up data. We analyzed renal function indicators before and after multiple treatments, comparing nephrotoxicity in patients receiving four cycles ("standard") with those receiving more than four ("extended treatment"). Nephrotoxicity was assessed via creatinine levels and CTCAE creatinine grades. Treatment effectiveness was gauged using Kaplan-Meier survival analysis, focusing on overall survival and disease-specific survival (DSS). Statistical analyses were performed using SPSS version 26 (IBM), R 4.2.3, and GraphPad Prism 9.0.0. Statistical significance was defined as a P-value of less than 0.05., Results: Our study cohort consisted of 281 patients in the standard group and 356 in the extended treatment group. No significant differences in baseline characteristics or renal function were noted between the two groups pre-treatment. Mean post-treatment creatinine levels did not significantly differ between the standard (89.30 ± 51.19 μmol/L) and extended treatment groups (93.20 ± 55.98 μmol/L; P = 0.364). Similarly, there was no statistical significance between the CTCAE creatinine grades of the two groups (P = 0.448). Adverse renal events were observed in 0.4% of patients in the standard group and 1.1% in the extended treatment group. After a median follow-up time of 88.3 months, we found that median overall survival was significantly higher in the extended treatment group (72.8 months) compared to the standard treatment group (52.8 months). A Cox regression analysis further supported these findings, indicating a better prognosis for the extended treatment group in terms of overall survival (HR: 0.580, P < 0.001) and DSS (HR: 0.599, P < 0.001)., Conclusion: Our findings suggest that extending PRRT treatment beyond the standard four cycles may be a safe and effective therapeutic strategy for NET patients. This approach could be particularly beneficial for patients experiencing disease recurrence or progression following standard treatment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Recent developments in 68 Ga-radiopharmaceuticals, including a number of regulatory approvals for clinical use, has created a hitherto unprecedented demand for 68 Ga. Reliable access to enough 68 Ga to meet growing clinical demand using only 68 Ge/ 68 Ga generators has been problematic in recent years. To address this challenge, we have optimized the direct production of 68 Ga on a cyclotron via the 68 Zn(p,n) 68 Ga reaction using a liquid target. This protocol describes the cyclotron-based production of [ 68 Ga]GaCl 3 implemented at the University of Michigan using a liquid target on GE PETtrace instrumentation. The protocol provides 56 ± 4 mCi (n = 3) of [ 68 Ga]GaCl 3 that meets the necessary quality control criteria to use for the preparation of 68 Ga-radiopharmaceuticals for human use., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)