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Simple Summary: Radioligand therapy plays a crucial role in the management of prostate cancer patients, for whom despite all available treatments, natural progression is almost inevitable. The failure of therapeutic options is likely to refer to the intrinsic tumor heterogeneity and the development of oncologic resistance pathways. To address this resistance, different trials are attempting to study the effectiveness and safety of combined therapies. This review provides a comprehensive overview of the current and future applications of radioligand therapy in prostate cancer from its initial application, moving towards future perspectives, and encompassing the main characteristics of ongoing trials related to this topic. In the last decades, the development of PET/CT radiopharmaceuticals, targeting the Prostate-Specific Membrane Antigen (PSMA), changed the management of prostate cancer (PCa) patients thanks to its higher diagnostic accuracy in comparison with conventional imaging both in staging and in recurrence. Alongside molecular imaging, PSMA was studied as a therapeutic agent targeted with various isotopes. In 2021, results from the VISION trial led to the Food and Drug Administration (FDA) approval of [177Lu]Lu-PSMA-617 as a novel therapy for metastatic castration-resistant prostate cancer (mCRPC) and set the basis for a radical change in the future perspectives of PCa treatment and the history of Nuclear Medicine. Despite these promising results, primary resistance in patients treated with single-agent [177Lu]Lu-PSMA-617 remains a real issue. Emerging trials are investigating the use of [177Lu]Lu-PSMA-617 in combination with other PCa therapies in order to cover the multiple oncologic resistance pathways and to overcome tumor heterogeneity. In this review, our aim is to retrace the history of PSMA-targeted therapy from the first preclinical studies to its future applications in PCa. [ABSTRACT FROM AUTHOR]

Background: Since most endocrine glands express ACE-2 receptors and can be infected by SARS-CoV-2 virus, this retrospective multicentre observational study aims to assess the metabolic activity of thyroid and adrenal glands of COVID-19 patients by 18F-FDG PET/CT. Methods: We retrospectively evaluated the 18F-FDG PET/CT scans of COVID-19 patients admitted by three different centres, either in a low-intensity department or in the intensive care unit (ICU). A visual assessment and a semi-quantitative evaluation of areas of interest in thyroid and adrenal glands were performed by recording SUVmax and SUVmean. The 18F-FDG PET/CT uptake in COVID-19 patients was compared with those observed in normal age-matched controls. Results: Between March 2020 and March 2022, 33 patients from three different centres (twenty-eight patients in a low-intensity department and five patients in ICU), were studied by 18F-FDG PET/CT during active illness. Seven of them were also studied after clinical remission (3–6 months after disease onset). Thirty-six normal subjects were used as age-matched controls. In the thyroid gland, no statistically significant differences were observed between control subjects and COVID-19 patients at diagnosis. However, at the follow-up PET/CT study, we found a statistically higher SUVmax and SUVmean (p = 0.009 and p = 0.004, respectively) in the thyroid of COVID-19 patients. In adrenal glands, we observed lower SUVmax and SUVmean in COVID-19 patients at baseline compared to control subjects (p < 0.0001) and this finding did not normalize after clinical recovery (p = 0.0018 for SUVmax and p = 0.002 for SUV mean). Conclusions: In our series, we observed persistent low 18F-FDG uptake in adrenal glands of patients at diagnosis of COVID-19 and after recovery, suggesting a chronic hypofunction. By contrast, thyroid uptake was comparable to normal subjects at disease onset, but after recovery, a subgroup of patients showed an increased metabolism, thus possibly suggesting the onset of an inflammatory thyroiditis. Our results should alert clinicians to investigate the pituitary–adrenal axis and thyroid functionality at the time of infection and to monitor them after recovery. [ABSTRACT FROM AUTHOR]

Background: To investigate the cause of lymphopenia in patients with newly diagnosed COVID-19, we measured [18F]FDG uptake in several tissues, including the ileum, right colon, and caecum at diagnosis and after recovery and correlated these measurements with haematological parameters. Methods: We studied, by [18F]FDG PET/CT, 18 newly diagnosed patients with COVID-19. Regions of interest were drawn over major organs and in the terminal ileum, caecum, and right colon, where the bowel wall was evaluable. Five patients were re-examined after recovery, and three of them also performed a white blood cell scan with 99mTc-HMPAO-WBC on both occasions. Complete blood count was performed on both occasions, and peripheral blood lymphocyte subsets were measured at diagnosis. Data were analysed by a statistician. Results: Patients had moderate severity COVID-19 syndrome. Basal [18F]FDG PET/CT showed focal lung uptake corresponding to hyperdense areas at CT. We also found high spleen, ileal, caecal, and colonic activity as compared to 18 control subjects. At recovery, hypermetabolic tissues tended to normalize, but activity in the caecum remained higher than in controls. Regression analyses showed an inverse correlation between CD4 + lymphocytes and [18F]FDG uptake in the caecum and colon and a direct correlation between CD8 + lymphocytes and [18F]FDG uptake in lungs and bone marrow. WBC scans showed the presence of leukocytes in the caecum and colon that disappeared at recovery. Conclusions: These findings indicate that lymphopenia in COVID-19 patients is associated with large bowel inflammation supporting the hypothesis that CD4 + lymphocytes migrate to peripheral lymphoid tissues in the bowel. [ABSTRACT FROM AUTHOR]

The article presents a case study on the use of 68Ga-DOTA0Tyr3octreotide (DOTA-TOC) positron emission tomography-computed tomography (PET/CT) in five patients with ectopic adrenocorticotropin (ACTH)-secreting (EAS) tumours of unkown origin. The patients underwent examination to identify the ectopic ACTH secretion source. All patients were found lesions expressing somatostatin receptors and the PET/CT detected EAS lung tumour in three patients.

Computed tomography (CT), 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), and hybrid FDG-PET/CT are the most commonly used diagnostic tools for the initial staging and treatment response assessment of lymphomas [1]. The aim of this report is to compare the correlations between functional imaging markers derived from FDG-PET/CT and whole-body, diffusion-weighted magnetic resonance imaging (DW-MRI) in a young patient affected by Hodgkin's lymphoma (HL). [ABSTRACT FROM AUTHOR]

Background: In neuroendocrine tumor (NET), complete surgery could better the prognosis. Radioguided surgery (RGS) with β - -radioisotopes is a novel approach focused on developing a new probe that, detecting electrons and operating with low background, provides a clearer delineation of the lesions with low radiation exposition for surgeons. As a first step to validate this procedure, ex vivo specimens of tumors expressing somatostatin receptors, as small intestine neuroendocrine tumor (SI-NET), were tested. Materials and Methods: SI-NET presents a high uptake of a beta-emitting radiotracer, 90 Y-DOTATOC. Five SI-NET patients were enrolled after performing a 68 Ga-DOTATOC positron emission tomography/computed tomography (CT) and a CT enterography; 24 h before surgery, they received 5 mCi of 90 Y-DOTATOC. Results: Surgery was performed as routine. Tumors and surrounding tissue were sectioned in different samples and examined ex vivo with the beta-detecting probe. All the tumor samples showed high counts of radioactivity that was up to a factor of 18 times higher than the corresponding cutoff value, with a sensitivity of 96% and a specificity of 100%. Conclusions: These first ex vivo RGS tests showed that this probe can discriminate very effectively between tumor and healthy tissues by the administration of low activities of 90 Y-DOTATOC, allowing more precise surgery.

A 35-year-old woman, already treated with surgery, chemotherapy, and radiotherapy for a ductal carcinoma of the left breast, underwent an (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) scan for an increase of the serum markers carcinoembryonic antigen (CEA) and cancer antigen 15.3 (CA15.3). The scan showed multiple FDG-avid lesions in the liver and bone. The images also detected two areas of uptake in the dorsal and lumbar spinal cord, which were suspicious for metastases; magnetic resonance imaging (MRI) confirmed these lesions.