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Background: 68 Ga-PSMA PET is the leading prostate cancer imaging technique, but the image quality remains noisy and could be further improved using an artificial intelligence-based denoising algorithm. To address this issue, we analyzed the overall quality of reprocessed images compared to standard reconstructions. We also analyzed the diagnostic performances of the different sequences and the impact of the algorithm on lesion intensity and background measures. Methods: We retrospectively included 30 patients with biochemical recurrence of prostate cancer who had undergone 68 Ga-PSMA-11 PET-CT. We simulated images produced using only a quarter, half, three-quarters, or all of the acquired data material reprocessed using the SubtlePET® denoising algorithm. Three physicians with different levels of experience blindly analyzed every sequence and then used a 5-level Likert scale to assess the series. The binary criterion of lesion detectability was compared between series. We also compared lesion SUV, background uptake, and diagnostic performances of the series (sensitivity, specificity, accuracy). Results: VPFX-derived series were classified differently but better than standard reconstructions (p < 0.001) using half the data. Q.Clear series were not classified differently using half the signal. Some series were noisy but had no significant effect on lesion detectability (p > 0.05). The SubtlePET® algorithm significantly decreased lesion SUV (p < 0.005) and increased liver background (p < 0.005) and had no substantial effect on the diagnostic performance of each reader. Conclusion: We show that the SubtlePET® can be used for 68 Ga-PSMA scans using half the signal with similar image quality to Q.Clear series and superior quality to VPFX series. However, it significantly modifies quantitative measurements and should not be used for comparative examinations if standard algorithm is applied during follow-up. [ABSTRACT FROM AUTHOR]

Simple Summary: Short, dysfunctional telomeres represent the genetic biomarkers of cancer. Studies in early-stage non-small-cell lung cancer (NSCLC) have shown that telomere length and telomerase levels are correlated with survival. In patients with advanced NSCLC, telomere status has not yet been investigated, and its clinical significance remains unknown. We studied telomere length and the expression of telomerase and shelterin genes in a cohort of 79 patients with advanced NSCLC, and evaluated these parameters as potential prognostic and predictive factors. Telomere shortening, high levels of telomerase and aberrant expression of shelterin genes TRF2, RAP1 and TIN2 were significantly correlated with shorter survival. Furthermore, a worse response to immunotherapy was observed in patients with shorter telomeres. The determination of telomere parameters in advanced NSCLC could be useful for individualized treatment decisions. Telomere length appears to correlate with survival in early non-small-cell lung cancer (NSCLC), but the prognostic impact of telomere status in advanced NSCLC remains undetermined. Our purpose was to evaluate telomere parameters as prognostic and predictive biomarkers in advanced NSCLC. In 79 biopsies obtained before treatment, we analyzed the telomere length and expression of TERT and shelterin complex genes (TRF1, TRF2, POT1, TPP1, RAP1, and TIN2), using quantitative PCR. Non-responders to first-line chemotherapy were characterized by shorter telomeres and low RAP1 expression (p = 0.0035 and p = 0.0069), and tended to show higher TERT levels (p = 0.058). In multivariate analysis, short telomeres were associated with reduced event-free (EFS, p = 0.0023) and overall survival (OS, p = 0.00041). TERT and TRF2 overexpression correlated with poor EFS (p = 0.0069 and p = 0.00041) and OS (p = 0.0051 and p = 0.007). Low RAP1 and TIN2 expression-levels were linked to reduced EFS (p = 0.00032 and p = 0.0069) and OS (p = 0.000051 and p = 0.02). Short telomeres were also associated with decreased survival after nivolumab therapy (p = 0.097). Evaluation of telomere status in advanced NSCLC emerges as a useful biomarker that allows for the selection of patient groups with different clinical evolutions, to establish personalized treatment. [ABSTRACT FROM AUTHOR]

With the emergence of disease modifying osteoarthritis drugs (DMOAD), imaging methods to quantitatively demonstrate their efficacy and to monitor osteoarthritis progression at the functional level are urgently needed. Our group showed that articular cartilage can be quantitatively assessed in nuclear medicine imaging by our radiotracer 99mTc-NTP 15-5 targeting cartilage proteoglycans. In this work, surgically induced DMM mice were treated with sprifermin or saline. We investigated cartilage remodelling in the mice knees by 99mTc-NTP 15-5 SPECT-CT imaging over 24 weeks after surgery, as wells as proteoglycan biochemical assays. OA alterations were scored by histology according to OARSI guidelines. A specific accumulation of 99mTc-NTP 15-5 in cartilage joints was evidenced in vivo by SPECT-CT imaging as early as 30 min post-iv injection. In DMM, 99mTc-NTP 15-5 accumulation in cartilage within the operated joints, relative to contralateral ones, was observed to initially increase then decrease as pathology progressed. Under sprifermin, 99mTc-NTP 15-5 uptake in pathological knees was significantly increased compared to controls, at 7-, 12- and 24-weeks, and consistent with proteoglycan increase measured 5 weeks post-surgery, as a sign of cartilage matrix remodelling. Our work highlights the potential of 99mTc-NTP 15-5 as an imaging-based companion to monitor cartilage remodelling in OA and DMOAD response. [ABSTRACT FROM AUTHOR]

Background: Benzamide-based radioligands targeting melanin were first developed for imaging melanoma and then for therapeutic purpose with targeted radionuclide therapy (TRT). [131I]ICF01012 presents a highly favorable pharmacokinetics profile in vivo for therapy. Tumour growth reduction and increase survival have been established in preclinical models of melanoma. According the these preclinical results, we initiate a first-in-human study aimed to determine the recommended dose of [131I]ICF01012 to administer for the treatment of patients with pigmented metastatic melanoma.Methods: The MELRIV-1 trial is an open-label, multicentric, dose-escalation phase I trial. The study is divided in 2 steps, a selection part with an IV injection of low activity of [131I]ICF01012 (185 MBq at D0) to select patients who might benefit from [131I]ICF01012 TRT in therapeutic part, i.e. patient presenting at least one tumour lesion with [131I]ICF01012 uptake and an acceptable personalized dosimetry to critical organs (liver, kidney, lung and retina). According to dose escalation scheme driven by a Continual Reassessment Method (CRM) design, a single therapeutic injection of 800 MBq/m2, or 1600 MBq/m2, or 2700 MBq/m2 or 4000 MBq/m2 of [131I]ICF01012 will be administered at D11 (± 4 days). The primary endpoint is the recommended therapeutic dose of [131I]ICF01012, with DLT defined as any grade 3-4 NCI-CT toxicity during the 6 weeks following therapeutic dose. Safety, pharmacokinetic, biodistribution (using planar whole body and SPECT-CT acquisitions), sensitivity / specificity of [131I]ICF01012, and therapeutic efficacy will be assessed as secondary objectives. Patients who received therapeutic injection will be followed until 3 months after TRT. Since 6 to 18 patients are needed for the therapeutic part, up to 36 patients will be enrolled in the selection part.Discussion: This study is a first-in-human trial evaluating the [131I]ICF01012 TRT in metastatic malignant melanomas with a diagnostic dose of the [131I]ICF01012 to select the patients who may benefit from a therapeutic dose of [131I]ICF01012, with at least one tumor lesion with [131I]ICF01012 uptake and an acceptable AD to healthy organ.Trial Registration: Clinicaltrials.gov : NCT03784625 . Registered on December 24, 2018. Identifier in French National Agency for the Safety of Medicines and Health Products (ANSM): N°EudraCT 2016-002444-17. [ABSTRACT FROM AUTHOR]

One of the current challenges in oncology is to develop imaging tools to early detect the response to conventional chemotherapy and adjust treatment strategies when necessary. Several studies evaluating PET imaging with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) as a predictive tool of therapeutic response highlighted its insufficient specificity and sensitivity. The [18F]FDG uptake reflects only tumor metabolic activity and not treatment-induced cell death, which seems to be relevant for therapeutic evaluation. Therefore, to evaluate this parameter in vivo , several cell death radiotracers have been developed in the last years. However, few of them have reached the clinical trials. This systematic review focuses on the use of [18F]ML-10 (2-(5-[18F]fluoropentyl)-2-methylmalonic acid) as radiotracer of apoptosis and especially as a measure of tumor response to treatment. A comprehensive literature review concerning the preclinical and clinical investigations conducted with [18F]ML-10 was performed. The abilities and applications of this radiotracer as well as its clinical relevance and limitations were discussed. Most studies highlighted a good ability of the radiotracer to target apoptotic cells. However, the increase in apoptosis during treatment did not correlate with the radiotracer tumoral uptake, even using more advanced image analysis (voxel-based analysis). [18F]ML-10 PET imaging does not meet current clinical expectations for early detection of the therapeutic response to conventional chemotherapy. This review has pointed out the challenges of applying various apoptosis imaging strategies in clinical trials, the current methodologies available for image analysis and the future of molecular imaging to assess this therapeutic response. [ABSTRACT FROM AUTHOR]

10.2967/jnumed.120.245738 8 Assadi M, Gholamrezanezhad A, Jokar N. Key elements of preparedness for pandemic coronavirus disease 2019 (COVID-19) in nuclear medicine units. Diagnostic scintigraphy procedures were most severely affected in the benign disease setting, with myocardial perfusion scintigraphy, ventilation lung scintigraphy, thyroid scintigraphy and bone scintigraphy suffering the greatest impact. Discussion Nuclear medicine departments were no exception with regard to the general influence of the COVID-19 pandemic on healthcare systems worldwide. Finally, while the scope of this survey was mainly focused on changes in healthcare in nuclear medicine units, the EANM, its national member societies and individual institutions are also the ones providing speciality training and academic research in nuclear medicine. [Extracted from the article]

Purpose: This study aims to perform dosimetry for [99mTc]NTP15‐5 radiotracer used in imaging of articular cartilage in rabbits and humans. The radiotracer (covered by a world patent WO 01/00621 A1) has been proposed in the previous years for the study of cartilage in osteoarthritis diseases. A sensitive imaging approach is essential to quantify osteoarthritis progression and monitor response to new therapies. [99mTc]NTP15‐5 binds to cartilage proteoglycans whose decreased content is associated to a loss of biomedical function of cartilage. We have implemented the whole dosimetry study concerning this new radiotracer for rabbits and humans using the GATE Monte Carlo platform. Materials and methods: Absorbed doses to critical organs are determined using the MIRD formalism. Biodistribution data are obtained by organ sampling, measuring the activity in organs for three rabbits sacrificed at various times postadministration, and by SPECT/CT imaging at different times after injection. Most important sources are cartilages (in knees and intervertebral discs), due to localization together with the liver and kidneys due to excretion of the agent. S‐values are calculated from rabbit's CT scan and human CT scan using the GATE v8.0 Monte Carlo platform. Cumulated activity in humans is extrapolated from animals using the %kg‐dose/g method. Particular attention is given to dose calculation in bones, bone marrow and organs at risk. Results: The dosimetry performed in rabbits shows highest absorbed doses for liver and kidneys with respectively 22.5 and 43.8 µGy per MBq of injected activity. In humans, we found absorbed doses for a maximum injected activity of 15 MBq/kg, that is, 1050 MBq for an adult of 70 kgs of 9.03 mGy for kidneys and 4.16 mGy for knee cartilages. Effective dose is 2.69 µSv/MBq. Conclusions: The dosimetry profile of [99mTc]NTP15‐5 in the context of preclinical trials is of major importance in order to make sure that organs at risk are not overexposed. GATE provides all the capability needed to calculate dose profiles for internal dosimetry. The extrapolation of the dose for a human model is a first step towards clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Loco regional persistence or recurrence of differentiated thyroid cancer (DTC) is frequent despite initial thyroidectomy and radioactive iodine therapy (RAI). The aim of this study was to analyze the impact of a complementary adjuvant RAI (Ad-RAI) on disease recurrence following re-operation on patients with locally persistent or recurrent DTC. Patients and Methods: A retrospective study of 85 patients with DTC was conducted. All patients were initially treated with total thyroidectomy and RAI, and re-operated for a locally persistent or recurrent disease. Propensity score was calculated to predict the impact of Ad-RAI on survival after reoperation, and to reduce the bias of the limited sample size and the prognostic tests. Results: 49 (58%) patients were re-treated with Ad-RAI after re-operation while 36 (42%) were only followed up. Disease recurrence after re-treatment (re-operation ± Ad-RAI) was detected in 31 patients (36.5%). In multivariate analysis, age >55 years (HR: 3.9 [1.6; 9.5]; p < 0.00001) was the main poor prognostic factor for recurrence-free survival. Three parameters independently influenced the decision to administer ad-RAI: low number of previous RAI administrations, Nx before re-operation, and pTg > 30 μg/l. These parameters were incorporated in the Propensity score calculation. If ad-RAI tended to improve recurrence-free survival (median survival 17.4 vs. 10.9 months), adjustment using the Propensity score removed any difference between the groups (p = 0.54), confirming the limited value of ad-RAI. Conclusion: In patients with locally persistent or recurrent DTC, age is the main independent prognostic factor. Adjuvant RAI does not improve recurrence-free survival of DTC patients. [ABSTRACT FROM AUTHOR]

Purpose: Dosimetry for melanoma‐targeted radionuclide therapy (TRT) with [131I]ICF01012, a melanin ligand, has been previously evaluated in mice bearing melanomas. In this study, activity distribution and dosimetry are performed on healthy rabbits (Fauve de Bourgogne) using SPECT‐CT imaging and ex vivo measurements. Material and Methods: Ex vivo biodistribution (i.v. injection: 370 kBq/kg, n = 2 per point) is performed on blood, eyes, brain, lung, liver, kidneys, heart, stomach, and spleen. Dosimetry calculations follow the MIRD formalism: S values are calculated from CT images using the GATE Monte Carlo platform and activity distributions are obtained from SPECT‐CT imaging (i.v. injection: 37 MBq/kg n = 3 per point). A specific study is presented to assess dose to human retina. Results: Time‐integrated activities based on SPECT‐CT are in accordance with ex vivo measurements except for spleen. Doses to liver and eyes are the most significant, with respectively, 6.38 ± 0.50 Gy/GBq (evaluated through SPECT‐CT imaging) and 45.8 ± 7.9 Gy/GBq (evaluated through ex vivo measurements). Characterization of ocular [131I]ICF01012 biodistribution in rabbits and quantification of melanin allowed to assess a dose of 3.07 ± 0.70 Gy/GBq to human retina. Conclusion: This study sustains [131I]ICF01012 as a good candidate for melanoma TRT and open perspectives for personalized dosimetry calculation during phase I clinical transfer. [ABSTRACT FROM AUTHOR]

Purpose: Here, we report a new and rapid radiosynthesis of F- N-[2-(diethylamino)ethyl]-6-fluoro-pyridine-3-carboxamide ([F]ICF01006), a molecule with a high specificity for melanotic tissue, and its evaluation in a murine model for early specific detection of pigmented primary and disseminated melanoma. Methods: [F]ICF01006 was synthesized using a new one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumour) or intravenous ( lung colonies) injection of B16BL6 melanoma cells in C57BL/6J mice. The relevance and sensitivity of positron emission tomography (PET) imaging using [F]ICF01006 were evaluated at different stages of tumoural growth and compared to F-fluorodeoxyglucose ([F]FDG). Results: The fully automated radiosynthesis of [F]ICF01006 led to a radiochemical yield of 61 % and a radiochemical purity >99 % (specific activity 70-80 GBq/μmol; total synthesis time 42 min). Tumours were visualized before they were palpable as early as 1 h post-injection with [F]ICF01006 tumoural uptake of 1.64 ± 0.57, 3.40 ± 1.47 and 11.44 ± 2.67 percentage of injected dose per gram of tissue (%ID/g) at days 3, 5 and 14, respectively. [F]ICF01006 PET imaging also allowed detection of melanoma pulmonary colonies from day 9 after tumour cell inoculation, with a lung radiotracer accumulation correlated with melanoma invasion. At day 21, radioactivity uptake in lungs reached a value of 5.23 ± 2.08 %ID/g (versus 0.41 ± 0.90 %ID/g in control mice). In the two models, comparison with [F]FDG showed that both radiotracers were able to detect melanoma lesions, but [F]ICF01006 was superior in terms of contrast and specificity. Conclusion: Our promising results provide further preclinical data, reinforcing the excellent potential of [F]ICF01006 PET imaging for early specific diagnosis and follow-up of melanin-positive disseminated melanoma. [ABSTRACT FROM AUTHOR]

Purpose: Preclinical data pointed to Tc-NTP 15-5 as a good candidate for single photon emission computed tomography (SPECT) imaging of cartilaginous disease. We set out to investigate and quantify Tc-NTP 15-5 ex vivo uptake by human articular cartilage relative to bone Tc-hydroxymethylene diphosphonate (HMDP) radiotracer. Methods: Three osteoarthritic human tibial plateaux and four tibiofemoral joints were incubated with Tc-NTP 15-5 and Tc-HMDP for 2 h. Affinity of tracers for cartilage was determined by visual analysis of SPECT/CT acquisitions and measurement of cartilage to cortical bone uptake ratios. Results: Cartilage to cortical bone uptake ratios were 3.90 ± 2.35 and 0.76 ± 0.24, respectively, for Tc-NTP 15-5 and Tc-HMDP radiotracers. Visual analysis of fused SPECT/CT slices showed selective, intense Tc-NTP 15-5 accumulation in articular cartilage, whereas Tc-HMDP binding was low. Interestingly, a cartilage defect visualized on CT was clearly associated with focal decreased uptake of Tc-NTP 15-5. Conclusion: The tracer Tc-NTP 15-5 is of major interest for human cartilage molecular imaging and could find clinical applications in osteoarthritis staging and monitoring. [ABSTRACT FROM AUTHOR]

(1) Background: As outcome of patients with metastatic melanoma treated with anti-PD1 immunotherapy can vary in success, predictors are needed. We aimed to predict at the patients' levels, overall survival (OS) and progression-free survival (PFS) after one year of immunotherapy, based on their pre-treatment 18F-FDG PET; (2) Methods: Fifty-six metastatic melanoma patients—without prior systemic treatment—were retrospectively included. Forty-five 18F-FDG PET-based radiomic features were computed and the top five features associated with the patient's outcome were selected. The analyzed machine learning classifiers were random forest (RF), neural network, naive Bayes, logistic regression and support vector machine. The receiver operating characteristic curve was used to compare model performances, which were validated by cross-validation; (3) Results: The RF model obtained the best performance after validation to predict OS and PFS and presented AUC, sensitivities and specificities (IC95%) of 0.87 ± 0.1, 0.79 ± 0.11 and 0.95 ± 0.06 for OS and 0.9 ± 0.07, 0.88 ± 0.09 and 0.91 ± 0.08 for PFS, respectively. (4) Conclusion: A RF classifier, based on pretreatment 18F-FDG PET radiomic features may be useful for predicting the survival status for melanoma patients, after one year of a first line systemic treatment by immunotherapy. [ABSTRACT FROM AUTHOR]