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Abstract Assessing the individual risk of Major Adverse Cardiac Events (MACE) is of major importance as cardiovascular diseases remain the leading cause of death worldwide. Quantitative Myocardial Perfusion Imaging (MPI) parameters such as stress Myocardial Blood Flow (sMBF) or Myocardial Flow Reserve (MFR) constitutes the gold standard for prognosis assessment. We propose a systematic investigation of the value of Artificial Intelligence (AI) to leverage [ $$^{82}$$ 82 Rb] Silicon PhotoMultiplier (SiPM) PET MPI for MACE prediction. We establish a general pipeline for AI model validation to assess and compare the performance of global (i.e. average of the entire MPI signal), regional (17 segments), radiomics and Convolutional Neural Network (CNN) models leveraging various MPI signals on a dataset of 234 patients. Results showed that all regional AI models significantly outperformed the global model ( $$p

Abstract Purpose To evaluate the effect of lung stabilization using high-frequency non-invasive ventilation (HF-NIV) and breath-hold (BH) techniques on lung nodule detection and texture assessment in PET/CT compared to a free-breathing (FB) standard lung CT acquisition in PET/CT. Materials and methods Six patients aged 65 ± 7 years, addressed for initial assessment of at least one suspicious lung nodule with 18F-FDG PET/CT, underwent three consecutive lung PET/CT acquisitions with FB, HF-NIV and BH. Lung nodules were assessed on all three CT acquisitions of the PET/CT and characterized for any size, volume and solid/sub-solid nature. Results BH detected a significantly higher number of nodules (n = 422) compared to HF-NIV (n = 368) and FB (n = 191) (p

Abstract First-line selective internal radiation therapy (SIRT) showed promising outcomes in patients with uveal melanoma liver metastases (UMLM). Patient survival depends on liver’s disease control. SIRT planning is essential and little is known about dosimetry. We investigated whether 99mTc-MAA-SPECT/CT dosimetry could predict absorbed doses (AD) evaluated on 90Y-PET/CT and assess the dose–response relationship in UMLM patients treated with first-line SIRT. This IRB-approved, single-center, retrospective analysis (prospectively collected cohort) included 12 patients (median age 63y, range 43–82). Patients underwent MRI/CT, 18F-FDG-PET/CT before and 3–6 months post-SIRT, and 90Y-PET/CT immediately post-SIRT. Thirty-two target lesions were included. AD estimates in tumor and non-tumor liver were obtained from 99mTc-MAA-SPECT/CT and post-SIRT 90Y-PET/CT, and assessed with Lin’s concordance correlation coefficients (ρ c and C b), Pearson’s coefficient correlation (ρ), and Bland–Altman analyses (mean difference ± standard deviation; 95% limits-of-agreement (LOA)). Influence of tumor characteristics and microsphere type on AD was analyzed. Tumor response was assessed according to size-based, enhancement-based and metabolic response criteria. Mean target lesion AD was 349 Gy (range 46–1586 Gy). Concordance between 99mTc-MAA-SPECT/CT and 90Y-PET/CT tumor dosimetry improved upon dose correction for the recovery coefficient (RC) (ρ = 0.725, ρ c = 0.703, C b = 0.969) with good agreement (mean difference: − 4.93 ± 218.3 Gy, 95%LOA: − 432.8–422.9). Without RC correction, concordance was better for resin microspheres (ρ = 0.85, ρ c = 0.998, C b = 0.849) and agreement was very good between predictive 99mTc-MAA-SPECT/CT and 90Y-PET/CT dosimetry (mean difference: − 4.05 ± 55.9 Gy; 95%LOA: − 113.7–105.6). After RC correction, 99mTc-MAA-SPECT/CT dosimetry overestimated AD (− 70.9 ± 158.9 Gy; 95%LOA: − 382.3–240.6). For glass microspheres, concordance markedly improved with RC correction (ρ = 0.790, ρ c = 0.713, C b = 0.903 vs without correction: ρ = 0.395, ρ c = 0.244, C b = 0.617) and 99mTc-MAA-SPECT/CT dosimetry underestimated AD (148.9 ± 267.5 Gy; 95%LOA: − 375.4–673.2). For non-tumor liver, concordance was good between 99mTc-MAA-SPECT/CT and 90Y-PET/CT dosimetry (ρ = 0.942, ρ c = 0.852, C b = 0.904). 99mTc-MAA-SPECT/CT slightly overestimated liver AD for resin (3.4 ± 3.4 Gy) and glass (11.5 ± 13.9 Gy) microspheres. Tumor AD was not correlated with baseline or post-SIRT lesion characteristics and no dose–response threshold could be identified. 99mTc-MAA-SPECT/CT dosimetry provides good estimates of AD to tumor and non-tumor liver in UMLM patients treated with first-line SIRT.

Abstract The development of diagnostic and therapeutic radiopharmaceuticals is an hot topic in nuclear medicine. Several radiolabeled antibodies are under development necessitating both biokinetic and dosimetry extrapolations for effective human translation. The validation of different animal-to-human dosimetry extrapolation methods still is an open issue. This study reports the mice-to-human dosimetry extrapolation of 64Cu/177Lu 1C1m-Fc anti-TEM-1 for theranostic application in soft-tissue sarcomas. We adopt four methods; direct mice-to-human extrapolation (M1); dosimetry extrapolation considering a relative mass scaling factor (M2), application of a metabolic scaling factor (M3) and combination of M2 and M3 (M4). Predicted in-human dosimetry for the [64Cu]Cu-1C1m-Fc resulted in an effective dose of 0.05 mSv/MBq. Absorbed dose (AD) extrapolation for the [177Lu]Lu-1C1m-Fc indicated that the AD of 2 Gy and 4 Gy to the red-marrow and total-body can be reached with 5–10 GBq and 25–30 GBq of therapeutic activity administration respectively depending on applied dosimetry method. Dosimetry extrapolation methods provided significantly different absorbed doses in organs. Dosimetry properties for the [64Cu]Cu-1C1m-Fc are suitable for a diagnostic in-human use. The therapeutic application of [177Lu]Lu-1C1m-Fc presents challenges and would benefit from further assessments in animals’ models such as dogs before moving into the clinic.

AimTo perform an international survey about PET/CT imaging with contrast enhanced CT (PET/ceCT) in clinical routine worldwide.MethodsA questionnaire of ten questions was prepared for health professionals, addressing the following issues: (1) general demographic, hospital, and department information; (2) use and diffusion of PET/ceCT worldwide; (3) factors influencing the use of PET/ceCT. An invitation to the survey was sent to the corresponding authors of NM scientific articles indexed in SCOPUS in 2022 and dedicated to PET/CT imaging. Data were analysed per individual responder.Results191 individual responders worldwide participated in this survey. Most of the responders are using PET/ceCT in their center (74%). Interestingly, the relative use of PET/ceCT over the total PET/CT scans has an anti-Gaussian distribution ( 80% ceCT were most represented). Most of responders are using PET/ceCT in oncological settings (62%) and irrespectively from radiopharmaceuticals (62%). In most cases, PET/ceCT scans are reported by NM physicians alone or together by NM physicians and radiologists with an integrated report (31%).ConclusionPET/ceCT imaging is largely used worldwide. Local factors can affect the choice of PET/ceCT in respect to conventional PET/CT imaging. Further cost–benefit analysis could be useful to consider other possible influencing variables, such as technologies, dosimetry, department organization and economics.

Abstract Background The primary aims of this study were to compare in patients with esophageal or esophagogastric junction cancers the potential of 68Ga-NODAGA-RGD PET/CT with that of 18F-FDG PET/CT regarding tumoral uptake and distribution, as well as histopathologic examination. Methods Ten 68Ga-NODAGA-RGD and ten 18F-FDG PET/CT were performed in nine prospectively included participants (1 woman; aged 58 ± 8.4 y, range 40–69 y). Maximum SUV (SUVmax) and metabolic tumor volumes (MTV) were calculated. The Mann–Whitney U test and Spearman correlation analysis (ρ) were used. Results 68Ga-NODAGA-RGD PET/CT detected positive uptake in 10 primary sites (8 for primary tumors and 2 for local relapse suspicion), 6 lymph nodes and 3 skeletal sites. 18F-FDG PET/CT detected positive uptake in the same sites but also in 16 additional lymph nodes and 1 adrenal gland. On a lesion-based analysis, SUVmax of 18F-FDG was significantly higher than those of 68Ga-NODAGA-RGD (4.9 [3.7–11.3] vs. 3.2 [2.6–4.2] g/mL, p = 0.014). Only one participant showed a higher SUVmax in an osseous metastasis with 68Ga-NODAGA-RGD as compared to 18F-FDG (6.6 vs. 3.9 g/mL). Correlation analysis showed positive correlation between 18F-FDG and 68Ga-NODAGA-RGD PET parameters (ρ = 0.56, p = 0.012 for SUVmax, ρ = 0.78, p

Abstract We report the case of a 72-year-old woman who presented with tuberculous arthritis during the setting of 177Lu-DOTATATE therapy for a grade-2 neuro-endocrine pancreatic tumor with liver metastases. We hypothesized that this recurrence might have been related to the occurrence of lymphopenia, which is common during PRRT. Indeed, though lymphopenia is frequently dismissed, it could lead to the development of opportunistic diseases and its severity should be examined, especially in case of abnormal clinical symptoms.

Abstract Background Quality and reproducibility of radiomics studies are essential requirements for the standardisation of radiomics models. As recent data-driven respiratory gating (DDG) [18F]-FDG has shown superior diagnostic performance in lung cancer, we evaluated the impact of DDG on the reproducibility of radiomics features derived from [18F]-FDG PET/CT in comparison to free-breathing flow (FB) imaging. Methods Twenty four lung nodules from 20 patients were delineated. Radiomics features were derived on FB flow PET/CT and on the corresponding DDG reconstruction using the QuantImage v2 platform. Lin’s concordance factor (C b ) and the mean difference percentage (DIFF%) were calculated for each radiomics feature using the delineated nodules which were also classified by anatomical localisation and volume. Non-reproducible radiomics features were defined as having a bias correction factor C b < 0.8 and/or a mean difference percentage DIFF% > 10. Results In total 141 features were computed on each concordance analysis, 10 of which were non-reproducible on all pulmonary lesions. Those were first-order features from Laplacian of Gaussian (LoG)-filtered images (sigma = 1 mm): Energy, Kurtosis, Minimum, Range, Root Mean Squared, Skewness and Variance; Texture features from Gray Level Cooccurence Matrix (GLCM): Cluster Prominence and Difference Variance; First-order Standardised Uptake Value (SUV) feature: Kurtosis. Pulmonary lesions located in the superior lobes had only stable radiomics features, the ones from the lower parts had 25 non-reproducible radiomics features. Pulmonary lesions with a greater size (defined as long axis length > median) showed a higher reproducibility (9 non-reproducible features) than smaller ones (20 non-reproducible features). Conclusion Calculated on all pulmonary lesions, 131 out of 141 radiomics features can be used interchangeably between DDG and FB PET/CT acquisitions. Radiomics features derived from pulmonary lesions located inferior to the superior lobes are subject to greater variability as well as pulmonary lesions of smaller size.

The management of prostate cancer is undergoing rapid changes in all disease settings. Novel imaging tools for diagnosis have been introduced, and the treatment of high-risk localized, locally advanced and metastatic disease has changed considerably in recent years. From clinical and health-economic perspectives, a rational and optimal use of the available options is of the utmost importance. While international guidelines list relevant pivotal trials and give recommendations for a variety of clinical scenarios, there is much room for interpretation, and several important questions remain highly debated. The goal of developing a national consensus on the use of these novel diagnostic and therapeutic strategies in order to improve disease management and eventually patient outcomes has prompted a Swiss consensus meeting. Experts from several specialties, including urology, medical oncology, radiation oncology, pathology and nuclear medicine, discussed and voted on questions of the current most important areas of uncertainty, including the staging and treatment of high-risk localized disease, treatment of metastatic hormone-sensitive prostate cancer (mHSPC) and use of new options to treat metastatic castration-resistant prostate cancer (mCRPC).

Background & Aims: Transarterial radioembolization (TARE) with Yttrium-90 resin microspheres is an established treatment option for patients with hepatocellular carcinoma (HCC). However, optimising treatment application and patient selection remains challenging. We report here on the effectiveness, safety and prognostic factors, including dosing methods, associated with TARE for HCC in the prospective observational CIRT study. Methods: We analysed 422 patients with HCC enrolled between Jan 2015 and Dec 2017, with follow-up visits every 3 months for up to 24 months after first TARE. Patient characteristics and treatment-related data were collected at baseline; adverse events and time-to-event data (overall survival [OS], progression-free survival [PFS] and hepatic PFS) were collected at every 3-month follow-up visit. We used the multivariable Cox proportional hazard model and propensity score matching to identify independent prognostic factors for effectiveness outcomes. Results: The median OS was 16.5 months, the median PFS was 6.1 months, and the median hepatic PFS was 6.7 months. Partition model dosimetry resulted in improved OS compared to body surface area calculations on multivariable analysis (hazard ratio 0.65; 95% CI 0.46-0.92; p = 0.0144), which was confirmed in the exact matching propensity score analysis (hazard ratio 0.56; 95% CI 0.35-0.89; p = 0.0136). Other independent prognostic factors for OS were ECOG-performance status >0 (p = 0.0018), presence of ascites (p = 0.0152), right-sided tumours (p = 0.0002), the presence of portal vein thrombosis (p = 0.0378) and main portal vein thrombosis (p = 0.0028), ALBI grade 2 (p = 0.0043) and 3 (p = 0.0014). Adverse events were recorded in 36.7% of patients, with 9.7% of patients experiencing grade 3 or higher adverse events. Conclusions: This large prospective observational dataset shows that TARE is an effective and safe treatment in patients with HCC. Using partition model dosimetry was associated with a significant improvement in survival outcomes. Impact and implications: Transarterial radioembolization (TARE) is a form of localised radiation therapy and is a potential treatment option for primary liver cancer. We observed how TARE was used in real-life clinical practice in various European countries and if any factors predict how well the treatment performs. We found that when a more complex but personalised method to calculate the applied radiation activity was used, the patient responded better than when a more generic method was used. Furthermore, we identified that general patient health, ascites and liver function can predict outcomes after TARE. Clinical trial number: NCT02305459.

PurposeTo investigate the emerging role of Tc-99m-labeled diphosphonate (Tc-99m-DPD) uptake quantification by SPECT/CT in fibrous dysplasia (FD) bone lesions and its correlation with biological bone turnover markers (BTMs) of disease activity.Materials and methodsSeven patients (49 ± 16 years) with a confirmed diagnosis of FD were included in this retrospective study. Bone scans with Tc-99m-DPD and quantitative SPECT/CT (xSPECT/CT) were performed. SUVmax (maximum standard unit value) and SUVmean (mean standard unit value) were measured in all FD bone lesions. The skeletal burden score (SBS) was assessed on planar scintigraphy and multiplied by mean SUVmax and SUVmean to generate two new parameters, SBS_SUVmax and SBS_SUVmean, respectively. Planar and xSPECT/CT quantitative measures were correlated with biological BTMs of disease activity, including fibroblast growth factor 23 (FGF-23), alkaline phosphatase (ALP), procollagen 1 intact N-terminal propeptide (P1NP) and C-terminal telopeptide (CTX), as well as scoliosis angle measured on radiographs. Statistical significance was evaluated with Spearman’s correlations.ResultsA total of 76 FD bone lesions were analyzed, showing an average SUVmax and SUVmean (g/mL) of 13 ± 7.3 and 8 ± 4.5, respectively. SBS, SBS_SUVmax and SBS_SUVmean values were 30.8 ± 25.6, 358 ± 267 and 220.1 ± 164.5, respectively. Mean measured values of FGF-23 (pg/mL), ALP (U/L), P1NP (μg/L) and CTX (pg/mL) were 98.4 (22–175), 283.5 (46–735), 283.1 (31–1,161) and 494 (360–609), respectively. Mean scoliosis angle was 15.7 (7–22) degrees. We found a very strong positive correlation between planar-derived SBS and CTX (r = 0.96, p = 0.010), but no significant correlation between SUVmax or SUVmean and biological BTMs. SBS_SUVmax showed a strong to very strong positive correlation with CTX (ρ = 0.99, p = 0.002), FGF-23 (ρ = 0.91, p = 0.010), ALP (ρ = 0.82, p = 0.020), and P1NP (ρ = 0.78, p = 0.039), respectively.ConclusionThis study showed that biological BTMs are significantly correlated with diphosphonate uptake on bone scan, quantified by a new parameter combining information from both planar and quantitative SPECT/CT. Further analysis of bone scan quantitative SPECT/CT data in a larger patient population might help better characterize the skeletal disease burden in FD, and guide treatment and follow-up.

Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy is a validated treatment option for patients with advanced prostate cancer. Although PSMA expression is not limited to prostate tissue, little is known about its relevance to other types of cancer. Here, we present a case report of a patient with uterine leiomyosarcoma that is progressing while on immunotherapy and treated with 177Lu-PSMA radionuclide therapy. We report for the first time that 177Lu-PSMA radionuclide therapy combined with immunotherapy outside of prostate cancer. We did observe post-treatment reduction of tumor growth rate, although we did not notice disease response based on RECIST criteria. We suggest that 177Lu-PSMA treatment especially combined with immunotherapy may be an option for patients with cancer without other therapeutic options. Insights: 177Lu-PSMA radionuclide therapy should be considered for any tumor stained positive for PSMA.

Abstract Background Integrin alpha-V-beta-3 (αvβ3) pathway is involved in intraplaque angiogenesis and inflammation and represents a promising target for molecular imaging in cardiovascular diseases such as atherosclerosis. The aim of this study was to assess the clinical correlates of arterial wall accumulation of 68Ga-NODAGA-RGD, a specific αvβ3 integrin ligand for PET. Materials and methods The data of 44 patients who underwent 68Ga-NODAGA-RGD PET/CT scans were retrospectively analyzed. Tracer accumulation in the vessel wall of major arteries was analyzed semi-quantitatively by blood-pool-corrected target-to-background ratios. Tracer uptake was compared with clinically documented atherosclerotic cardiovascular disease, cardiovascular risk factors and calcified plaque burden. Data were compared using the Mann–Whitney U test, Pearson correlation and Spearman correlation. Results 68Ga-NODAGA-RGD arterial uptake was significantly higher in patients with previous clinically documented atherosclerotic cardiovascular disease (mean TBR 2.44 [2.03–2.55] vs. 1.81 [1.56–1.96], p = 0.001) and showed a significant correlation with prior cardiovascular or cerebrovascular event (r = 0.33, p = 0.027), BMI (ρ = 0.38, p = 0.01), plaque burden (ρ = 0.31, p = 0.04) and hypercholesterolemia (r = 0.31, p = 0.04). Conclusions 68Ga-NODAGA-RGD holds promise as a non-invasive marker of disease activity in atherosclerosis, providing information about intraplaque angiogenesis.

The abscopal effect describes the ability of locally administered radiotherapy to induce systemic antitumor effects. Although mentioned for the first time in the 1950s, records of abscopal effects, considered to be immune-mediated, are scarce with radiotherapy alone. However, with the continued development and use of immunotherapy, reports on the abscopal effect have become increasingly frequent during the last decade. Here, we report a patient with advanced malignant pleural mesothelioma who had progressive disease while on the anti-PDL1 inhibitor pembrolizumab and showed an abscopal response after palliative radiotherapy.

Studies using arginine–glycine–aspartate (RGD)-PET agents in cardiovascular diseases have been recently published. The aim of this systematic review was to perform an updated, evidence-based summary about the role of RGD-based PET agents in patients with cardiovascular diseases to better address future research in this setting. Original articles within the field of interest reporting the role of RGD-based PET agents in patients with cardiovascular diseases were eligible for inclusion in this systematic review. A systematic literature search of PubMed/MEDLINE and Cochrane library databases was performed until October 26, 2021. Literature shows an increasing role of RGD-based PET agents in patients with cardiovascular diseases. Overall, two main topics emerged: the infarcted myocardium and atherosclerosis. The existing studies support that αvβ3 integrin expression in the infarcted myocardium is well evident in RGD PET/CT scans. RGD-based PET radiotracers accumulate at the site of infarction as early as 3 days and seem to be peaking at 1–3 weeks post myocardial infarction before decreasing, but only 1 study assessed serial changes of myocardial RGD-based PET uptake after ischemic events. RGD-based PET uptake in large vessels showed correlation with CT plaque burden, and increased signal was found in patients with prior cardiovascular events. In human atherosclerotic carotid plaques, increased PET signal was observed in stenotic compared with non-stenotic areas based on MR or CT angiography data. Histopathological analysis found a co-localization between tracer accumulation and areas of αvβ3 expression. Promising applications using RGD-based PET agents are emerging, such as prediction of remodeling processes in the infarcted myocardium or detection of active atherosclerosis, with potentially significant clinical impact.

Abstract Interventional radiology plays an important and increasing role in cancer treatment. Follow-up is important to be able to assess treatment success and detect locoregional and distant recurrence and recommendations for follow-up are needed. At ECIO 2018, a joint ECIO-ESOI session was organized to establish follow-up recommendations for oncologic intervention in liver, renal, and lung cancer. Treatments included thermal ablation, TACE, and TARE. In total five topics were evaluated: ablation in colorectal liver metastases (CRLM), TARE in CRLM, TACE and TARE in HCC, ablation in renal cancer, and ablation in lung cancer. Evaluated modalities were FDG-PET-CT, CT, MRI, and (contrast-enhanced) ultrasound. Prior to the session, five experts were selected and performed a systematic review and presented statements, which were voted on in a telephone conference prior to the meeting by all panelists. These statements were presented and discussed at the ECIO-ESOI session at ECIO 2018. This paper presents the recommendations that followed from these initiatives. Based on expert opinions and the available evidence, follow-up schedules were proposed for liver cancer, renal cancer, and lung cancer. FDG-PET-CT, CT, and MRI are the recommended modalities, but one should beware of false-positive signs of residual tumor or recurrence due to inflammation early after the intervention. There is a need for prospective preferably multicenter studies to validate new techniques and new response criteria. This paper presents recommendations that can be used in clinical practice to perform the follow-up of patients with liver, lung, and renal cancer who were treated with interventional locoregional therapies.

Abstract Background Angiogenesis plays an important role in head and neck squamous cell carcinoma (HNSCC) progression. This pilot study was designed to compare the distribution of 68Ga-NODAGA-RGD PET/CT for imaging αvβ3 integrins involved in tumor angiogenesis to 18F-FDG PET/CT in patients with HNSCC. Material and methods Ten patients (aged 58.4 ± 8.3 years [range, 44–73 years], 6 males, 4 females) with a total of 11 HNSCC were prospectively enrolled. Activity mapping and standard uptake values (SUV) from both 68Ga-NODAGA-RGD and 18F-FDG PET/CT scans were recorded for primary tumor and compared with the Wilcoxon signed-rank test. The relation between the SUV of both tracers was assessed using the Spearman correlation. Results All HNSCC tumors were visible with both tracers. Quantitative analysis showed higher 18F-FDG SUVmax in comparison to 68Ga-NODAGA-RGD (14.0 ± 6.1 versus 3.9 ± 1.1 g/mL, p = 0.0017) and SUVmean (8.2 ± 3.1 versus 2.0 ± 0.8 g/mL, p = 0.0017). Both 18F-FDG and 68Ga-NODAGA-RGD uptakes were neither correlated with grade, HPV status nor p16 protein expression (p ≥ 0.17). Conclusion All HNSCC tumors were detected with both tracers with higher uptake with 18F-FDG, however. 68Ga-NODAGA-RGD has a different spatial distribution than 18F-FDG bringing different tumor information. Trial registration NCT, NCT02666547 . Registered 12.8.2012.

Abstract Background The folate receptor alpha (FRα) is an interesting target for imaging and therapy of different cancers. We present the first in-human radiation dosimetry and radiation safety results acquired within a prospective, multicentric trial (NCT03242993) evaluating the 18F-AzaFol (3′-aza-2′-[18F]fluorofolic acid) as the first clinically assessed PET tracer targeting the FRα. Material and methods Six eligible patients presented a histologically confirmed adenocarcinoma of the lung with measurable lesions (≥ 10 mm according to RECIST 1.1). TOF-PET images were acquired at 3, 11, 18, 30, 40, 50, and 60 min after the intravenous injection of 327 MBq (range 299–399 MBq) of 18F-AzaFol to establish dosimetry. Organ absorbed doses (AD), tumor AD, and patient effective doses (E) were assessed using the OLINDA/EXM v.2.0 software and compared with pre-clinical results. Results No serious related adverse events were observed. The highest AD were in the liver, the kidneys, the urinary bladder, and the spleen (51.9, 45.8, 39.1, and 35.4 μGy/MBq, respectively). Estimated patient and gender-averaged E were 18.0 ± 2.6 and 19.7 ± 1.4 μSv/MBq, respectively. E in-human exceeded the value of 14.0 μSv/MBq extrapolated from pre-clinical data. Average tumor AD was 34.8 μGy/MBq (range 13.6–60.5 μGy/MBq). Conclusions 18F-Azafol is a PET agent with favorable dosimetric properties and a reasonable radiation dose burden for patients which merits further evaluation to assess its performance. Trial registration ClinicalTrial.gov , NCT03242993 , posted on August 8, 2017

Abstract Purpose Bone scintigraphy with 99mTc-labeled diphosphonates can identify prostate cancer bone metastases with high sensitivity, but relatively low specificity, because benign conditions such as osteoarthritis can also trigger osteoblastic reactions. We aimed to investigate the diagnostic performance of 99mTc-2,3-dicarboxy propane-1,1-diphosphonate (99mTc-DPD) uptake quantification by single-photon emission computed tomography coupled with computed tomography (SPECT/CT) for distinguishing prostate cancer bone metastases from spinal and pelvic osteoarthritic lesions. Methods We retrospectively assessed 26 bone scans from 26 patients with known prostate cancer bone metastases and 13 control patients with benign spinal and pelvic osteoarthritic changes without known neoplastic disease. Quantitative SPECT/CT (xSPECT, Siemens Symbia Intevo, Erlangen, Germany) was performed and standardized uptake values (SUVs) were quantified with measurements of SUVmax and SUVmean (g/mL) in all bone metastases for the prostate cancer group and in spinal and pelvic osteoarthritic changes for the control group. We used receiver operating characteristics (ROC) curves to determine the optimum SUVmax cutoff value to distinguish between bone metastases and benign spinal and pelvic lesions. Results In total, 264 prostate cancer bone metastases were analyzed, showing a mean SUVmax and SUVmean of 34.6 ± 24.6 and 20.8 ± 14.7 g/mL, respectively. In 24 spinal and pelvic osteoarthritic lesions, mean SUVmax and SUVmean were 14.2 ± 3.8 and 8.9 ± 2.2 g/mL, respectively. SUVmax and SUVmean were both significantly different between the bone metastases and osteoarthritic groups (p ≤ 0.0001). Using a SUVmax cutoff of 19.5 g/mL for prostate cancer bone metastases in the spine and pelvis, sensitivity, specificity, positive and negative predictive values were 87, 92, 99 and 49%, respectively. Conclusion This study showed significant differences in quantitative 99mTc-DPD uptake on bone SPECT/CT between prostate cancer bone metastases and spinal and pelvic osteoarthritic changes, with higher SUVmax and SUVmean in metastases. Using a SUVmax cutoff of 19.5 g/mL, high specificity and positive predictive value for metastases identification in the spine and pelvis were found, thus increasing accuracy of bone scintigraphy.

Arising from the biliary tract, cholangiocarcinoma is a rare and aggressive epithelial cancer. According to the primary site, it can be further classified into intrahepatic, perihilar and distal types. Due to the lack of symptoms early in the disease course, most patients are diagnosed at advanced stages. Being not candidates for curative surgical management, these patients are treated with palliative systemic chemotherapy, and their prognosis remains poor. Using radioisotopes like yttrium-90 -labeled microspheres (90Y), radioembolization represents a local approach to treat primary and secondary liver tumors. In the case of intrahepatic cholangiocarcinoma, radioembolization can be used as a primary treatment, as an adjunct to chemotherapy or after failing chemotherapy. An 88-year-old man underwent radioembolization for a previously untreated stage II intrahepatic cholangiocarcinoma. One week later, he presented to our clinic with a non-pruritic maculopapular rash of the lower extremities and abdomen, worsening fatigue and low-grade fever. Laboratory exams, including hepatitis screening, were within normal limits. Showing positive immunofluorescence staining for immunoglobulin M (IgM) and complement 3 (C3) in vessel walls without IgA involvement, the skin biopsy results were compatible with leukocytoclastic vasculitis. Apart from the anticancer intervention, there have been no recent medication changes which could explain this complication. Notably, we did not observe any side effects during or after the perfusion scan with technetium-99m macroaggregated albumin (MAA) performed prior to radioembolization. The symptoms resolved quickly after a short course of colchicine and did not reappear at cholangiocarcinoma progression. In the absence of other evident causes, we conclude that the onset of leukocytoclastic vasculitis in our patient was directly linked to the administration of yttrium-90 -labeled microspheres. Our report therefore demonstrates that this condition can be a rare but manageable complication of 90Y liver radioembolization.

Mesothelioma is a malignancy of serosal membranes. Parietal pleura is the most common site, with peritoneum being the second most frequent location. Malignant peritoneal mesothelioma (MPM) is a rare and aggressive disease. The prognosis is often very poor with median overall survival ranging from 6 to 18 months in patients who are not candidates for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) due to non-resectable disease or comorbid conditions. For patients with resectable disease, CRS and HIPEC have become the standard of care. However, for patients with unresectable malignant mesothelioma there is unfortunately no effective systemic treatment beyond the first line. Based on the results of a recent phase II trial, lurbinectedin has clinical activity and acceptable toxicity in the second- and third-line treatment of malignant pleural mesothelioma. However, until present, no data have been available for patients with MPM and for patients who become refractory after multiple treatment lines. We report on two patients with metastatic MPM who achieved durable disease control of 10+ and 8 months with lurbinectedin in the fourth and fifth treatment line, respectively.

Abstract Background Biodistribution studies based on organ harvesting represent the gold standard pre-clinical technique for dose extrapolations. However, sequential imaging is becoming increasingly popular as it allows the extraction of longitudinal data from single animals, and a direct correlation with deterministic radiation effects. We assessed the feasibility of mouse-specific, microPET-based dosimetry of an antibody fragment labeled with the positron emitter 152Tb [(T 1/2 = 17.5 h, Eβ+mean = 1140 keV (20.3%)]. Image-based absorbed dose estimates were compared with those obtained from the extrapolation to 152Tb of a classical biodistribution experiment using the same antibody fragment labeled with 111In. 152Tb was produced by proton-induced spallation in a tantalum target, followed by mass separation and cation exchange chromatography. The endosialin-targeting scFv78-Fc fusion protein was conjugated with the chelator p-SCN-Bn-CHX-A”-DTPA, followed by labeling with either 152Tb or 111In. Micro-PET images of four immunodeficient female mice bearing RD-ES tumor xenografts were acquired 4, 24, and 48 h after the i.v. injection of 152Tb-CHX-DTPA-scFv78-Fc. After count/activity camera calibration, time-integrated activity coefficients (TIACs) were obtained for the following compartments: heart, lungs, liver, kidneys, intestines, tumor, and whole body, manually segmented on CT. For comparison, radiation dose estimates of 152Tb-CHX-DTPA-scFv78-Fc were extrapolated from mice dissected 4, 24, 48, and 96 h after the injection of 111In-CHX-DTPA-scFv78-Fc (3–5 mice per group). Imaging-derived and biodistribution-derived organ TIACs were used as input in the 25 g mouse model of OLINDA/EXM® 2.0, after appropriate mass rescaling. Tumor absorbed doses were obtained using the OLINDA2 sphere model. Finally, the relative percent difference (RD%) between absorbed doses obtained from imaging and biodistribution were calculated. Results RD% between microPET-based dosimetry and biodistribution-based dose extrapolations were + 12, − 14, and + 17 for the liver, the kidneys, and the tumors, respectively. Compared to biodistribution, the imaging method significantly overestimates the absorbed doses to the heart and the lungs (+ 89 and + 117% dose difference, respectively). Conclusions MicroPET-based dosimetry of 152Tb is feasible, and the comparison with organ harvesting resulted in acceptable dose discrepancies for body districts that can be segmented on CT. These encouraging results warrant additional validation using radiolabeled biomolecules with a different biodistribution pattern.

We are continuously progressing in our understanding of cancer and other diseases and learned how they can be heterogeneous among patients. Therefore, there is an increasing need for accurate characterization of diseases at the molecular level. In parallel, medical imaging and image-guided therapies are rapidly developing fields with new interventions and procedures entering constantly in clinical practice. Theranostics, a relatively new branch of medicine, refers to procedures combining diagnosis and treatment, often based on patient and disease-specific features or molecular markers. Interventional oncology which is at the convergence point of diagnosis and treatment employs several methods related to theranostics to provide minimally invasive procedures tailored to the patient characteristics. The aim is to develop more personalized procedures able to identify cancer cells, selectively reach and treat them, and to assess drug delivery and uptake in real-time in order to perform adjustments in the treatment being delivered based on obtained procedure feedback and ultimately predict response. Here, we review several interventional oncology procedures referring to the field of theranostics, and describe innovative methods that are under development as well as future directions in the field.

1C1m-Fc, an anti-tumor endothelial marker 1 (TEM-1) scFv-Fc fusion protein antibody, was previously successfully radiolabeled with 177Lu. TEM-1 specific tumor uptake was observed together with a non-saturation dependent liver uptake that could be related to the number of dodecane tetraacetic acid (DOTA) chelator per 1C1m-Fc. The objective of this study was to verify this hypothesis and to find the best DOTA per 1C1m-Fc ratio for theranostic applications. 1C1m-Fc was conjugated with six concentrations of DOTA. High-pressure liquid chromatography, mass spectrometry, immunoreactivity assessment, and biodistribution studies in mice bearing TEM-1 positive tumors were performed. A multi-compartment pharmacokinetic model was used to fit the data and a global pharmacokinetic model was developed to illustrate the effect of liver capture and immunoreactivity loss. Organ absorbed doses in mice were calculated from biodistribution results. A loss of immunoreactivity was observed with the highest DOTA per 1C1m-Fc ratio. Except for the spleen and bone, an increase of DOTA per 1C1m-Fc ratio resulted in an increase of liver uptake and absorbed dose and a decrease of uptake in tumor and other tissues. Pharmacokinetic models correlated these results. The number of DOTA per antibody played a determining role in tumor targeting. One DOTA per 1C1m-Fc gave the best pharmacokinetic behavior for a future translation of [177Lu]Lu-1C1m-Fc in patients.

Background: Infectious endocarditis is a life-threatening disease, requiring prompt and accurate diagnosis. The aim of this article is to perform a systematic review and meta-analysis of the literature to estimate the performance of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for the diagnosis of native valve endocarditis (NVE). Methods: Selected articles evaluating the diagnostic accuracy of 18F-FDG PET/CT in patients with suspected NVE, resulting from a comprehensive literature search through the PubMed/MEDLINE and Cochrane library databases until April 2020, were included for the systematic review and meta-analysis. Results: Seven studies (351 episodes of suspected NVE) were included. 18F-FDG PET/CT yielded a pooled sensitivity of 36.3% and a pooled specificity of 99.1% for the diagnosis of NVE. The pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 8.3, 0.6, and 15.3, respectively. The sensitivity increased using contemporary PET/CT device with state-of-the-art patient preparation as well as innovative image acquisitions or adding the results of 18F-FDG PET/CT in a multimodality strategy. Conclusions: In our systematic review and meta-analysis, 18F-FDG PET/CT yielded a poor pooled sensitivity with an otherwise excellent pooled specificity for the diagnosis of NVE; however, several factors may increase the sensitivity without affecting the specificity and these factors should be better evaluated in future studies.

INTRODUCTION:Aim was to develop a full automatic clustering approach of the time-activity curves (TAC) from dynamic 18F-FET PET and evaluate its association with IDH1 mutation status and survival in patients with gliomas. METHODS:Thirty-seven patients (mean age: 45±13 y) with newly diagnosed gliomas and dynamic 18F-FET PET before any histopathologic investigation or treatment were retrospectively included. Each dynamic 18F-FET PET was realigned to the first image and spatially normalized in the Montreal Neurological Institute template. A tumor mask was semi-automatically generated from Z-score maps. Each brain tumor voxel was clustered in one of the 3 following centroids using dynamic time warping and k-means clustering (centroid #1: slowly increasing slope; centroid #2: rapidly increasing followed by slowly decreasing slope; and centroid #3: rapidly increasing followed by rapidly decreasing slope). The percentage of each dynamic 18F-FET TAC within tumors and other conventional 18F-FET PET parameters (maximum and mean tumor-to-brain ratios [TBRmax and TBRmean], time-to-peak [TTP] and slope) was compared between wild-type and IDH1 mutant tumors. Their prognostic value was assessed in terms of progression free-survival (PFS) and overall survival (OS) by Kaplan-Meier estimates. RESULTS:Twenty patients were IDH1 wild-type and 17 IDH1 mutant. Higher percentage of centroid #1 and centroid #3 within tumors were positively (P = 0.016) and negatively (P = 0.01) correlated with IDH1 mutated status. Also, TBRmax, TBRmean, TTP, and slope discriminated significantly between tumors with and without IDH1 mutation (P range 0.01 to 0.04). Progression occurred in 22 patients (59%) at a median of 13.1 months (7.6-37.6 months) and 13 patients (35%) died from tumor progression. Patients with a percentage of centroid #1 > 90% had a longer survival compared with those with a percentage of centroid #1 < 90% (P = 0.003 for PFS and P = 0.028 for OS). This remained significant after stratification on IDH1 mutation status (P = 0.029 for PFS and P = 0.034 for OS). Compared to other conventional 18F-FET PET parameters, TTP and slope were associated with PFS and OS (P range 0.009 to 0.04). CONCLUSIONS:Based on dynamic 18F-FET PET acquisition, we developed a full automatic clustering approach of TAC which appears to be a valuable noninvasive diagnostic and prognostic marker in patients with gliomas.

INTRODUCTION:Amino-acids positron emission tomography (PET) is increasingly used in the diagnostic workup of patients with gliomas, including differential diagnosis, evaluation of tumor extension, treatment planning and follow-up. Recently, progresses of computer vision and machine learning have been translated for medical imaging. Aim was to demonstrate the feasibility of an automated 18F-fluoro-ethyl-tyrosine (18F-FET) PET lesion detection and segmentation relying on a full 3D U-Net Convolutional Neural Network (CNN). METHODS:All dynamic 18F-FET PET brain image volumes were temporally realigned to the first dynamic acquisition, coregistered and spatially normalized onto the Montreal Neurological Institute template. Ground truth segmentations were obtained using manual delineation and thresholding (1.3 x background). The volumetric CNN was implemented based on a modified Keras implementation of a U-Net library with 3 layers for the encoding and decoding paths. Dice similarity coefficient (DSC) was used as an accuracy measure of segmentation. RESULTS:Thirty-seven patients were included (26 [70%] in the training set and 11 [30%] in the validation set). All 11 lesions were accurately detected with no false positive, resulting in a sensitivity and a specificity for the detection at the tumor level of 100%. After 150 epochs, DSC reached 0.7924 in the training set and 0.7911 in the validation set. After morphological dilatation and fixed thresholding of the predicted U-Net mask a substantial improvement of the DSC to 0.8231 (+ 4.1%) was noted. At the voxel level, this segmentation led to a 0.88 sensitivity [95% CI, 87.1 to, 88.2%] a 0.99 specificity [99.9 to 99.9%], a 0.78 positive predictive value: [76.9 to 78.3%], and a 0.99 negative predictive value [99.9 to 99.9%]. CONCLUSIONS:With relatively high performance, it was proposed the first full 3D automated procedure for segmentation of 18F-FET PET brain images of patients with different gliomas using a U-Net CNN architecture.

Background: Diagnostic performance of positron emission tomography using white blood cells labeled with fluorine-18-fluorodeoxyglucose (18F-FDG-WBC PET or PET/CT) in patients with suspicious infectious diseases has been evaluated in several studies; however, there is no consensus about the diagnostic accuracy of this method. Therefore, a systematic review and meta-analysis was carried out on this topic. Methods: A comprehensive computer literature search screening PubMed/MEDLINE, Embase and Cochrane library databases through March 2019 was performed. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR−), and diagnostic odds ratio (DOR) of 18F-FDG-WBC PET or PET/CT in patients with infectious diseases were calculated. Results: Eight studies on the use of 18F-FDG-WBC PET or PET/CT in suspicious infectious diseases were discussed in the systematic review. The meta-analysis of seven studies (236 patients) provided these pooled results on a per patient-based analysis: sensitivity was 86.3% [95% confidence interval (95%CI) 75−92.9%], specificity 92% (95%CI 79.8−97.1%), LR+ 6.6 (95%CI: 3.1−14.1), LR− 0.2 (95%CI: 0.12−0.33), DOR 43.5 (95%CI: 12.2−155). A statistically significant heterogeneity was not detected. Conclusions: Despite limited literature data, 18F-FDG-WBC PET or PET/CT demonstrated a good diagnostic accuracy for the diagnosis of infectious diseases; nevertheless, larger studies are needed.