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Angiogenesis is an essential part of the cardiac repair process after myocardial infarction, but its spatiotemporal dynamics remain to be fully deciphered. 68 Ga-NODAGA-Arg-Gly-Asp (RGD) is a PET tracer targeting α v β 3 integrin expression, which is a marker of angiogenesis. Methods: In this prospective single-center trial, we aimed to monitor angiogenesis through myocardial integrin α v β 3 expression in 20 patients with ST-segment elevation myocardial infarction (STEMI). In addition, the correlations between the expression levels of myocardial α v β 3 integrin and the subsequent changes in 82 Rb PET/CT parameters, including rest and stress myocardial blood flow (MBF), myocardial flow reserve (MFR), and wall motion abnormalities, were assessed. The patients underwent 68 Ga-NODAGA-RGD PET/CT and rest and stress 82 Rb-PET/CT at 1 wk, 1 mo, and 3 mo after STEMI. To assess 68 Ga-NODAGA-RGD uptake, the summed rest 82 Rb and 68 Ga-NODAGA-RGD images were coregistered, and segmental SUVs were calculated (RGD SUV). Results: At 1 wk after STEMI, 19 participants (95%) presented increased 68 Ga-NODAGA-RGD uptake in the infarcted myocardium. Seventeen participants completed the full imaging series. The values of the RGD SUV in the infarcted myocardium were stable 1 mo after STEMI (1 wk vs. 1 mo, 1.47 g/mL [interquartile range (IQR), 1.37-1.64 g/mL] vs. 1.47 g/mL [IQR, 1.30-1.66 g/mL]; P = 0.9), followed by a significant partial decrease at 3 mo (1.32 g/mL [IQR, 1.12-1.71 g/mL]; P = 0.011 vs. 1 wk and 0.018 vs. 1 mo). In segment-based analysis, positive correlations were found between RGD SUV at 1 wk and the subsequent changes in stress MBF (Spearman ρ: r = 0.17, P = 0.0033) and MFR (Spearman ρ: r = 0.31, P < 0.0001) at 1 mo. A negative correlation was found between RGD SUV at 1 wk and the subsequent changes in wall motion abnormalities at 3 mo (Spearman ρ: r = - 0.12, P = 0.035). Conclusion: The present study found that α v β 3 integrin expression is significantly increased in the infarcted myocardium 1 wk after STEMI. This expression remains stable after 1 mo and partially decreases after 3 mo. Initial α v β 3 integrin expression at 1 wk is significantly weakly correlated with subsequent improvements in stress MBF, MFR, and wall motion analysis., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

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 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 < 0.001 ), where the best AUC of 73.9% (CI 72.5-75.3) was obtained with a CNN model. A regional AI model based on MBF averages from 17 segments fed to a Logistic Regression (LR) constituted an excellent trade-off between model simplicity and performance, achieving an AUC of 73.4% (CI 72.3-74.7). A radiomics model based on intensity features revealed that the global average was the least important feature when compared to other aggregations of the MPI signal over the myocardium. We conclude that AI models can allow better personalized prognosis assessment for MACE., (© 2024. The Author(s).)

Background: 18 F-FDG PET/CT is performed for the assessment of radioactive iodine non-avid disease in patients with DTC. In patients prepared by THW, increased pituitary uptake of 18 F-FDG in the absence of pituitary disease may reflect the physiological activation of pituitary thyrotroph cells by hypothyroidism. This study aimed to compare pituitary 18 F-FDG uptake in patients with DTC under THW vs. rhTSH stimulation., Methods: A total of 57 patients with DTC undergoing 18 F-FDG PET/CT (40 under THW and 17 under rhTSH stimulation) were retrospectively analyzed. Pituitary metabolism was expressed as maximum standardized uptake value (SUVmax) and as SUVratio using the right cerebellum as reference., Results: Pituitary hypermetabolism (SUVmax ≥ 4.1) was present in more patients in the THW group compared to the rhTSH group (62.5% vs. 23.5%; p = 0.01). Pituitary metabolism was significantly higher in the THW group compared to the rhTSH group, as assessed by either SUVmax (mean ± SD: 4.61 ± 1.22, 95%CI: 4.22-5.00 vs. 3.34 ± 0.86, 95%CI: 2.9-3.8; p < 0.001) or SUVratio (0.52 ± 0.11, 95%CI: 0.49-0.56 vs. 0.42 ± 0.07, 95%CI: 0.38-0.46; p < 0.001). Serum TSH levels correlated positively with SUVmax (r = 0.41, p < 0.01) and SUVratio (r = 0.44, p < 0.01) in the THW group only., Conclusions: The present findings support the hypothesis that pituitary hypermetabolism on 18 F-FDG PET/CT in patients with DTC undergoing THW is a common physiological response to hypothyroidism. Awareness of this physiological hypermetabolism is important to avoid potential pitfalls in image interpretation.

Nervous system metastases (CNSm) are late events associated with poor outcomes in endocrine-sensitive HER2-negative breast cancer (BC) patients, especially in the presence of leptomeningeal disease (LMD). Effective treatments are extremely limited in this setting. The antibody-drug conjugate, trastuzumab-deruxtecan (T-DXd), which combines the anti-HER2 antibody trastuzumab with a topoisomerase type 1 inhibitor, showed high efficacy not only against HER2-positive but also HER2-low metastatic BCs, expressing HER2 at a lower level. To the best of our knowledge, this is the first report of a patient with metastatic endocrine-sensitive HER2-low BC suffering from BMs associated with LMD and sustained disease control when treated with T-DXd. Several recent case series have reported the activity of T-DXd in patients with HER2-positive disease and brain metastases or LMD, but none in HER2-low patients. This case is particularly relevant since more than 50% of BCs are HER2-low., Competing Interests: Benita Wolf, Vincent Dunet, Estelle Dubruc, Marie Nicod Lalonde, and Luis Schiappacasse declare no conflicts of interest; Ana Dolcan: Advisory Boards for Novartis and PharmaMar and support for participation in congresses by PharmaMar and Lilly; Khalil Zaman: Advisory Boards for AstraZeneca, Daiichi, Exact Sciences, Gilead, Lilly, MSD, Mylan, Novartis, Pierre Fabre, and Seagen. Research funding: Roche; support for participation in international congresses: AstraZeneca, Daiichi, Gilead, Pierre Fabre, Roche. Unrestricted funding for organization of academic symposium: Agendia, AstraZeneca-MSD, Daiichi, Eisai, Exact Sciences, Lilly, Pierre Fabre, Gilead, Novartis, Pfizer, Roche, Seagen, Viatris/Mylan, Vifor., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Aim: To perform an international survey about PET/CT imaging with contrast enhanced CT (PET/ceCT) in clinical routine worldwide., Methods: A 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., Results: 191 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 (<20% ceCT and > 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%)., Conclusion: PET/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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Annunziata, Testart, Auf der Springe, Cuzzocrea, Nicod Lalonde, Schaefer, Prior, Garibotto and Treglia.)

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 18 F-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 < 0.001). The mean nodule size (mm) was 2.4 ± 2.1, 2.6 ± 1.9 and 3.2 ± 2.4 in BH, HF-NIV and FB, respectively, for long axis and 1.5 ± 1.3, 1.6 ± 1.2 and 2.1 ± 1.7 in BH, HF-NIV and FB, respectively, for short axis. Long- and short-axis diameters were significantly different between BH and FB (p < 0.001) and between HF-NIV and FB (p < 0.001 and p = 0.008), but not between BH and HF-NIV. A trend for higher volume was shown in FB compared to BH (p = 0.055) and HF-NIV (p = 0.068) without significant difference between BH and HF-NIV (p = 1). We found a significant difference in detectability of sub-solid nodules between the three acquisitions, with BH showing a higher number of sub-solid nodules (n = 128) compared to HF-NIV (n = 72) and FB (n = 44) (p = 0.002)., Conclusion: We observed a higher detection rate of pulmonary nodules on CT under BH or HF-NIV conditions applied to PET/CT than with FB. BH and HF-NIV demonstrated comparable texture assessment and performed better than FB in assessing size and volume. BH showed a better performance for detecting sub-solid nodules compared to HF-NIV and FB. The addition of BH or HF-NIV to PET/CT can help improve the detection and texture characterization of lung nodules by CT, therefore improving the accuracy of oncological lung disease assessment. The ease of use of BH and its added value should prompt its use in routine practice., (© 2023. Springer Nature Switzerland AG.)

Mutations in isocitrate dehydrogenase (IDH) represent an independent predictor of better survival in patients with gliomas. We aimed to assess grade and IDH mutation status in patients with untreated gliomas, by evaluating the respective value of 18 F-FET PET/CT via dynamic and texture analyses. A total of 73 patients (male: 48, median age: 47) who underwent an 18 F-FET PET/CT for initial glioma evaluation were retrospectively included. IDH status was available in 61 patients (20 patients with WHO grade 2 gliomas, 41 with grade 3-4 gliomas). Time-activity curve type and 20 parameters obtained from static analysis using LIFEx© v6.30 software were recorded. Respective performance was assessed using receiver operating characteristic curve analysis and stepwise multivariate regression analysis adjusted for patients' age and sex. The time-activity curve type and texture parameters derived from the static parameters showed satisfactory-to-good performance in predicting glioma grade and IDH status. Both time-activity curve type (stepwise OR: 101.6 (95% CI: 5.76-1791), p = 0.002) and NGLDM coarseness (stepwise OR: 2.08 × 10 43 (95% CI: 2.76 × 10 12 -1.57 × 10 74 ), p = 0.006) were independent predictors of glioma grade. No independent predictor of IDH status was found. Dynamic and texture analyses of 18 F-FET PET/CT have limited predictive value for IDH status when adjusted for confounding factors. However, they both help predict glioma grade.

The aim of this prospective pilot study was to evaluate the feasibility of a new hybrid imaging modality, free-hand single-photon computed tomography/ultrasonography (fhSPECT/US), for preoperative localization of parathyroid adenomas and to compare its performance with conventional ultrasonography and SPECT/CT. Twelve patients diagnosed with primary hyperparathyroidism underwent sequentially US and parathyroid scintigraphy, including SPECT/CT, followed by fhSPECT/US, allowing for real-time fusion between US and freehand-generated gamma-camera images. The fhSPECT/US detection rates were correlated with histopathology, when available, or with the imaging modality showing the most lesions. Based on a per patient analysis, the detection rate was significantly different when comparing SPECT/CT to fhSPECT/US ( p = 0.03), and not significantly different when comparing SPECT/CT to US ( p = 0.16) and US to fhSPECT/US ( p = 0.08). Based on a per-lesion analysis, the detection rate of SPECT/CT was significantly higher than that of US ( p = 0.01) and fhSEPCT/US ( p = 0.003), and there was no significant difference in detection rate when comparing US to fhSPECT/US ( p = 0.08). The main perceived limitations of fhSPECT/US in lesion detection were: (i) lesions localized at a depth ≥4.5 cm; (ii) imperfect image fusion due to tissue compression; (iii) limited spatial manipulation ability of the SPECT mobile camera handheld probe; and (iv) a wide spread of detected activity. In conclusion, clinical use of fhSPECT/US for localization of parathyroid adenomas is feasible, but shows lower sensitivity than conventional modalities and requires technical improvements.

Background: The primary aims of this study were to compare in patients with esophageal or esophagogastric junction cancers the potential of 68 Ga-NODAGA-RGD PET/CT with that of 18 F-FDG PET/CT regarding tumoral uptake and distribution, as well as histopathologic examination., Methods: Ten 68 Ga-NODAGA-RGD and ten 18 F-FDG PET/CT were performed in nine prospectively included participants (1 woman; aged 58 ± 8.4 y, range 40-69 y). Maximum SUV (SUV max ) and metabolic tumor volumes (MTV) were calculated. The Mann-Whitney U test and Spearman correlation analysis (ρ) were used., Results: 68 Ga-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. 18 F-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, SUV max of 18 F-FDG was significantly higher than those of 68 Ga-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 SUV max in an osseous metastasis with 68 Ga-NODAGA-RGD as compared to 18 F-FDG (6.6 vs. 3.9 g/mL). Correlation analysis showed positive correlation between 18 F-FDG and 68 Ga-NODAGA-RGD PET parameters (ρ = 0.56, p = 0.012 for SUV max , ρ = 0.78, p < 0.001 for lesion-to-background ratios and ρ = 0.58, p = 0.024 for MTV). We observed that 18 F-FDG uptake was homogenous inside all the confirmed primary sites (n = 9). In contrast, 68 Ga-NODAGA-RGD PET showed more heterogenous uptake in 6 out of the 9 confirmed primary sites (67%), seen mostly in the periphery of the tumor in 5 out of the 9 confirmed primary sites (56%), and showed slight extensions into perilesional structures in 5 out of the 9 confirmed primary sites (56%)., Conclusions: In conclusion, 68 Ga-NODAGA-RGD has lower potential in the detection of esophageal or esophagogastric junction malignancies compared to 18 F-FDG. However, the results suggest that PET imaging of integrin α v β 3 expression may provide complementary information and could aid in tumor diversity and delineation., Trial Registration: Trial registration: NCT02666547. Registered January 28, 2016-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02666547 ., (© 2023. The Author(s).)

Background: There is no consensus on how to predict post-transplant function of donation after circulatory death ( DCD ) kidneys. Thus, we aimed to identify renal scintigraphy parameters that could predict 1-year kidney function., Methods: In this single center study, we included all consecutive DCD kidney recipients between 2013 and 2021 ( n  = 29). Patients who did not have a scintigraphy within 10 days of transplantation ( n  = 3), recipients of multiple organs and less than 18 years old were excluded ( n  = 1). Primary endpoint was the estimated glomerular filtration rate (eGFR)., Results: Median eGFR and serum creatinine at 1 year were 67 µmol/L (56-81) and 111 ml/min (99-132), respectively. Among parameters tested, the 3rd/2nd-minute activity ratio had the best diagnostic performance (AUC: 0.74 and 0.71, for eGFR and creatinine) 1 year post transplantation. Using 1.21 as the best cut off, the 3rd/2nd-minute activity ratio specificity and sensitivity to predict eGFR >60 ml/min was 0.82 and 0.83. Renal function was significantly better at 1 week, 3, 6, and 12 months after transplantation in patients with 3rd/2nd-minute activity ratios above 1.21., Conclusion: This study suggests that the 3rd/2nd-minute activity ratio can predict graft function at 1 year. The benefit of post-transplant scintigraphy should be further validated in a prospective cohort., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Belhoste, Allenbach, Agius, Meier, Venetz, Corpataux, Schneider, Golshayan, Prior, Déglise, Nicod-Lalonde and Longchamp.)

Purpose: To 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 Methods: Seven 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. SUV max (maximum standard unit value) and SUV mean (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 SUV max and SUV mean to generate two new parameters, SBS&#95;SUV max and SBS&#95;SUV mean , 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., Results: A total of 76 FD bone lesions were analyzed, showing an average SUV max and SUV mean (g/mL) of 13 ± 7.3 and 8 ± 4.5, respectively. SBS, SBS&#95;SUV max and SBS&#95;SUV mean 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 SUV max or SUV mean and biological BTMs. SBS&#95;SUV max 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., Conclusion: This 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jreige, Hall, Becce, Aubry-Rozier, Gonzalez Rodriguez, Schaefer, Prior and Nicod Lalonde.)

Background: Quality and reproducibility of radiomics studies are essential requirements for the standardisation of radiomics models. As recent data-driven respiratory gating (DDG) [ 18 F]-FDG has shown superior diagnostic performance in lung cancer, we evaluated the impact of DDG on the reproducibility of radiomics features derived from [ 18 F]-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., (© 2022. The Author(s).)

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 α v β 3 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 α v β 3 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dietz, Kamani, Dunet, Fournier, Rubimbura, Testart Dardel, Schaefer, Jreige, Boughdad, Nicod Lalonde, Schaefer, Mewton, Prior and Treglia.)

Background: The manifestation of Graves' disease (GD) in patients treated with radioactive iodine (RAI) for hyperfunctioning thyroid nodules (RAI-induced GD or post-RAI GD) remains a long-standing challenge in radionuclide therapy. Known risk factors for post-RAI GD include preexisting subclinical hyperthyroidism, positive thyroid peroxidase autoantibodies (TPOAb), positive TSH receptor autoantibodies (TRAb) or otherwise undiagnosed GD. However, these risk factors are not present in all patients with post-RAI GD, and therefore it cannot always be predicted in a reliable manner if a given patient has a high risk for RAI-induced GD or not., Case Presentation: We describe the case of a 64 year-old woman known for hyperthyroidism due to toxic nodular goiter; she was treated initially with carbimazole, and then, due to recurrence, underwent RAI treatment. Three months later, symptomatic hyperthyroidism persisted. Diagnosis of new-onset GD was made based on typical ultrasound findings and newly-positive TRAb. Our patient had only positive thyroglobulin antibodies (TgAb) before RAI treatment, whereas TPOAb were negative., Conclusions: In the literature, TgAb have never been reported as a possible risk factor for RAI-induced GD. The present case suggests that the assessment for pre-existing autoimmunity in patients considering RAI for hyperfunctioning thyroid nodules should probably also include TgAb., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rouiller, Nicod Lalonde and Sykiotis.)

Oligometastatic disease (OMD) is an emerging state of disease with limited metastatic tumor burden. It should be distinguished from polymetastatic disease due the potential curative therapeutic options of OMD. Imaging plays a pivotal role in the diagnosis and follow-up of patients with OMD. The imaging tools needed in the case of OMD will differ according to different parameters, which include primary tumor type, timing between measurement and treatment, potential metastatic location and the patient's individual risk for metastasis. In this article, OMD is defined and the use of different imaging modalities in several oncologic situations are described in order to better understand OMD and its specific implication for radiologists.

Background: Immune checkpoint inhibitor (ICI)-related myocarditis is a rare but potentially fatal adverse event that can occur following ICI exposure. Early diagnosis and treatment are key to improve patient outcomes. Somatostatin receptor-based positron emission tomography-CT (PET/CT) showed promising results for the assessment of myocardial inflammation, yet information regarding its value for the diagnosis of ICI-related myocarditis, especially at the early stage, is limited. Thus, we investigated the value of 68 Ga-DOTA(0)-Phe(1)-Tyr(3)-octreotide ( 68 Ga-DOTATOC) PET/CT for the early detection and diagnosis of ICI-related myocarditis., Methods: Consecutive patients with clinically suspected ICI-related myocarditis from July 2018 to February 2021 were retrospectively evaluated in this single-center study. All patients underwent imaging for the detection of ICI-related myocarditis using either cardiac magnetic resonance (CMR) imaging or 68 Ga-DOTATOC PET/CT. PET/CT images were acquired 90 min after the injection of 2 MBq/kg 68 Ga-DOTATOC with pathological myocardial uptake in the left ventricle (LV) suggestive of myocarditis defined using a myocardium-to-background ratio of peak standard uptake value to mean intracavitary LV standard uptake (MBR peak ) value above 1.6. Patients had a full cardiological work-up including ECG, echocardiography, serum cardiac troponin I (cTnI), cardiac troponin T and creatine kinase (CK), CK-MB. Endomyocardial biopsy and inflammatory cytokine markers were also analyzed. The detection rate of ICI-related myocarditis using 68 Ga-DOTATOC PET/CT and CMR was assessed., Results: A total of 11 patients had clinically suspected ICI-related myocarditis; 9 underwent 68 Ga -DOTATOC PET/CT. All nine (100%) patients with 68 Ga-DOTATOC PET/CT presented with pathological myocardial uptake in the LV that was suggestive of myocarditis (MBR peak of 3.2±0.8, range 2.2-4.4). Eight patients had CMR imaging and 3/8 (38%) patients had lesions evocative of myocarditis. All PET-positive patients were previously treated with a high dose of steroids and intravenous immunoglobulin prior to PET/CT had elevated serum cTnI except for one patient for whom PET/CT was delayed several days. Interestingly, in 5/6 (83%) patients who presented with concomitant myositis, pathological uptake was seen on whole-body 68 Ga-DOTATOC PET/CT images in the skeletal muscles, suggesting an additional advantage of this method to assess the full extent of the disease. In contrast, four patients with CMR imaging had negative findings despite having elevated serum cTnI levels (range 20.5-5896.1 ng/mL), thus defining possible myocarditis. Newly identified immune correlates could provide specific biomarkers for the diagnosis of ICI-related myocarditis. Most tested patients (six of seven patients) had serum increases in the inflammatory cytokine interleukin (IL)-6 and in the chemokines CXCL9, CXCL10, and CXCL13, and the mass cytometry phenotypes of immune cell populations in the blood also showed correlations with myocardial inflammation. Four of five patients with myocarditis exhibited a Th1/Th2 imbalance favoring a pronounced inflammatory Th1, Th1/Th17, and Th17 CD4 memory T-cell response. The high proportion of non-classical monocytes and significantly reduced levels of CD31 in four to five patients was also consistent with an inflammatory disease., Conclusion: The use of 68 Ga-DOTATOC PET/CT along with immune correlates is a highly sensitive method to detect ICI-related myocarditis especially in the early stage of myocardial inflammation, as patients with elevated cTnI may present normal CMR imaging results. 68 Ga-DOTATOC PET/CT is also useful for detecting concomitant myositis. These results need to be confirmed in a larger population of patients and validated against a histological gold standard if available., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Desmoid-type fibromatosis (DTF) is a very rare variant of papillary thyroid carcinoma (PTC). It is essentially a dual tumor with a component of classical PTC with malignant epithelial proliferation ( BRAF -mutated) and another component of mesenchymal proliferation ( CTNNB1 -mutated). We conducted a literature review on PTC-DTF. In total, 31 articles were identified, that together reported on 54 patients. The mean age was 47 years, with a 2.2:1 female predominance. No ultrasound features were found to be helpful in differentiating PTC-DTF from other PTC variants. Of the 43 cases that reported histological details, 60% had locally infiltrative disease (T3b or T4). Around 48% had cervical lymph node metastases, but none had distant metastases. While PTC-DTF may be locally more aggressive than classic PTC, its overall behavior is similar and can include extrathyroidal extension and lymph node metastases, which may contain a stromal component and show extranodal invasion. The mainstay of treatment for PTC-DTF is surgery, and the DTF component is not expected to be sensitive to radioactive iodine. External radiotherapy, non-steroidal anti-inflammatory drugs, tyrosine kinase inhibitors and chemotherapy have also been used in selected cases. Due to the rarity of these tumors and the lack of specific treatment guidelines, management should be discussed in a multidisciplinary team.

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 68 Ga-NODAGA-RGD, a specific α v β 3 integrin ligand for PET., Materials and Methods: The data of 44 patients who underwent 68 Ga-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: 68 Ga-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: 68 Ga-NODAGA-RGD holds promise as a non-invasive marker of disease activity in atherosclerosis, providing information about intraplaque angiogenesis., (© 2021. The Author(s).)

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 ( 18 F-FDG PET/CT) for the diagnosis of native valve endocarditis (NVE)., Methods: Selected articles evaluating the diagnostic accuracy of 18 F-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. 18 F-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 18 F-FDG PET/CT in a multimodality strategy., Conclusions: In our systematic review and meta-analysis, 18 F-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.

On conventional PET/CT, and under physiological conditions, the volume of the pituitary gland (PG) is small, and its metabolic activity is commonly comparable to the surrounding background level in 18 F-FDG imaging. We compared the physiological 18 F-FDG uptake of the PG in patients imaged with digital PET (dPET) and with conventional PET (cPET). Additionally, we performed phantom experiments to characterize signal recovery and detectability of small structures. We retrospectively included 10 dPET and 10 cPET patients and measured PG SUVmax, SUVmean and SUVratio (using cerebellum as reference). We imaged a modified NEMA/IEC phantom with both dPET and cPET (background activity 5 kBq/mL, and 3× and 5× higher concentrations in ∅2-20-mm spherical inserts). Mean recovery coefficients (RCmean) and signal-difference-to-noise-ratio (SDNR) were computed to assess lesion detectability. Patients imaged with dPET presented higher PG SUVmax and SUVratio (SUVR) compared to patients imaged with cPET (4.7 ± 2.05 vs. 2.9 ± 0.64, p = 0.004; and 0.62 ± 0.25 vs 0.39 ± 0.09, p = 0.029, respectively), while there was no difference for SUVmean (2.7 ± 1.32 vs 2.1 ± 0.44, p = 0.39). Thus, with a SUV readout scale of 0-5 g/mL, normal PG appeared abnormally hot with dPET, but not with cPET. Phantom evidenced higher RCmean in dPET compared to cPET. For both 3x and 5x measurements, lesion detectability according to size was systematically superior with dPET. In conclusion, patients imaged with dPET presented higher 18 F-FDG physiological uptake of the PG as compared to patients imaged with cPET. These findings were supported by phantom experiments demonstrating superior signal recovery and small region detectability with dPET. Awareness of this new "higher" SUV of the normal 18 F-FDG uptake of the PG is important to avoid potential pitfalls in image interpretation, notably in oncologic patients treated with immunotherapy, who are at increased risk to develop hypophysitis.

Purpose: Bone scintigraphy with 99m Tc-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 99m Tc-2,3-dicarboxy propane-1,1-diphosphonate ( 99m Tc-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 SUV max and SUV mean (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 SUV max 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 SUV max and SUV mean of 34.6 ± 24.6 and 20.8 ± 14.7 g/mL, respectively. In 24 spinal and pelvic osteoarthritic lesions, mean SUV max and SUV mean were 14.2 ± 3.8 and 8.9 ± 2.2 g/mL, respectively. SUV max and SUV mean were both significantly different between the bone metastases and osteoarthritic groups (p ≤ 0.0001). Using a SUV max 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 99m Tc-DPD uptake on bone SPECT/CT between prostate cancer bone metastases and spinal and pelvic osteoarthritic changes, with higher SUV max and SUV mean in metastases. Using a SUV max 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.

Background: Tumor-induced or oncogenic osteomalacia (TIO) is a rare paraneoplastic syndrome in which osteomalacia is a consequence of fibroblast growth factor 23 (FGF23) secretion by a mesenchymal tumor. The localization of the culprit lesion in patients with TIO is often challenging. Several studies have evaluated the detection rate (DR) of these tumors using somatostatin receptor positron emission tomography (SSTR-PET/CT). We aimed to summarize literature findings on this topic providing pooled estimates of DR., Methods: A comprehensive literature search by screening PubMed, Embase and Cochrane library electronic databases through August 2019 was performed. The pooled DR of culprit tumors using SSTR-PET/CT in patients with TIO was calculated using a random-effects statistical model., Results: Fourteen studies on the use of SSTR-PET/CT in detecting the culprit tumor in patients with TIO were included in the qualitative analysis. The pooled DR of SSTR-PET/CT on a per-patient-based analysis calculated using eleven studies (166 patients) was 87.6% (95% confidence interval (95% CI) 80.2-95.1%). Statistical heterogeneity among studies was detected (I-square = 63%), likely due to the use of different radiolabeled somatostatin analogues, as demonstrated by a subgroup analysis., Conclusions: Despite limited literature data due to the rarity of the disease, SSTR-PET/CT demonstrated a very high DR of culprit tumors in patients with TIO and it could be used as first-line imaging method for this indication., Competing Interests: The authors declare no conflicts of interest.

Background: Diagnostic performance of positron emission tomography using white blood cells labeled with fluorine-18-fluorodeoxyglucose ( 18 F-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 18 F-FDG-WBC PET or PET/CT in patients with infectious diseases were calculated., Results: Eight studies on the use of 18 F-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, 18 F-FDG-WBC PET or PET/CT demonstrated a good diagnostic accuracy for the diagnosis of infectious diseases; nevertheless, larger studies are needed.

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., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To generate a predictive whole-liver radiomics scoring system for progression-free survival (PFS) and overall survival (OS) in patients undergoing transarterial radioembolization using Yttrium-90 ( 90 Y-TARE) for unresectable hepatocellular carcinoma (uHCC)., Results: The generated pPET-RadScores were significantly correlated with survival for PFS (median of 11.4 mo [95% confidence interval CI: 6.3-16.5 mo] in low-risk group [PFS-pPET-RadScore < 0.09] vs. 4.0 mo [95% CI: 2.3-5.7 mo] in high-risk group [PFS-pPET-RadScore > 0.09]; P = 0.0004) and OS (median of 20.3 mo [95% CI: 5.7-35 mo] in low-risk group [OS-pPET-RadScore < 0.11] vs. 7.7 mo [95% CI: 6.0-9.5 mo] in high-risk group [OS-pPET-RadScore > 0.11]; P = 0.007). The multivariate analysis confirmed PFS-pPET-RadScore ( P = 0.006) and OS-pPET-RadScore ( P = 0.001) as independent negative predictors., Conclusion: Pretreatment 18 F-FDG PET whole-liver radiomics signature appears as an independent negative predictor for PFS and OS in patients undergoing 90 Y-TARE for uHCC., Methods: Pretreatment 18 F-FDG PET of 47 consecutive patients undergoing 90 Y-TARE for uHCC (31 resin spheres, 16 glass spheres) were retrospectively analyzed. For each patient, based on PET radiomics signature from whole-liver semi-automatic segmentation, PFS and OS predictive PET-radiomics scores (pPET-RadScores) were obtained using LASSO Cox regression. Using X-tile software, the optimal score to predict PFS (PFS-pPET-RadScore) and OS (OS-pPET-RadScore) served as cutoff to separate high and low-risk patients. Survival curves were estimated using the Kaplan-Meier method. The prognostic value of PFS and OS-pPET-RadScore, Barcelona-Clinic Liver Cancer staging system and serum alpha-fetoprotein level was analyzed to predict PFS and OS in multivariate analysis., Competing Interests: CONFLICTS OF INTEREST The authors have no potential conflicts of interest to report.

Background: For the past decade (18)F-fluoro-ethyl-l-tyrosine (FET) and (18)F-fluoro-deoxy-glucose (FDG) positron emission tomography (PET) have been used for the assessment of patients with brain tumor. However, direct comparison studies reported only limited numbers of patients. Our purpose was to compare the diagnostic performance of FET and FDG-PET., Methods: We examined studies published between January 1995 and January 2015 in the PubMed database. To be included the study should: (i) use FET and FDG-PET for the assessment of patients with isolated brain lesion and (ii) use histology as the gold standard. Analysis was performed on a per patient basis. Study quality was assessed with STARD and QUADAS criteria., Results: Five studies (119 patients) were included. For the diagnosis of brain tumor, FET-PET demonstrated a pooled sensitivity of 0.94 (95% CI: 0.79-0.98) and pooled specificity of 0.88 (95% CI: 0.37-0.99), with an area under the curve of 0.96 (95% CI: 0.94-0.97), a positive likelihood ratio (LR+) of 8.1 (95% CI: 0.8-80.6), and a negative likelihood ratio (LR-) of 0.07 (95% CI: 0.02-0.30), while FDG-PET demonstrated a sensitivity of 0.38 (95% CI: 0.27-0.50) and specificity of 0.86 (95% CI: 0.31-0.99), with an area under the curve of 0.40 (95% CI: 0.36-0.44), an LR+ of 2.7 (95% CI: 0.3-27.8), and an LR- of 0.72 (95% CI: 0.47-1.11). Target-to-background ratios of either FDG or FET, however, allow distinction between low- and high-grade gliomas (P > .11)., Conclusions: For brain tumor diagnosis, FET-PET performed much better than FDG and should be preferred when assessing a new isolated brain tumor. For glioma grading, however, both tracers showed similar performances., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)