Alessandra Guercio

Sustainability in healthcare, particularly Nuclear Medicine, is essential, especially in managing radioactive materials. Traditional centralized production

Background: Localization of recurrent or residual insulinoma may be particularly challenging in postoperative setting, especially in the presence of postoperative anatomical distortion and inconclusive conventional imaging. Case Presentation: A 71‐year‐old man developed recurrent endogenous hyperinsulinemic hypoglycemia following apparently curative surgical enucleation of a pancreatic insulinoma. The postoperative course was complicated by intra‐abdominal hemorrhage and pseudocyst formation, resulting in marked anatomical distortion. Despite persistent biochemical evidence of insulinoma recurrence, serial contrast–enhanced computed tomography (CT) and ⁶⁸ Ga‐DOTATOC PET/CT failed to identify residual disease. Subsequent glucagon‐like peptide‐1 receptor (GLP‐1R) imaging with ⁶⁸ Ga‐NODAGA‐Exendin‐4 PET/CT demonstrated focal tracer uptake in the pancreatic head, highly suggestive of recurrent or residual insulinoma. Endoscopic ultrasound (EUS) subsequently confirmed a small lesion in the uncinate process, which was successfully treated with EUS–guided radiofrequency ablation (EUS‐RFA). Following the procedure, hypoglycemic episodes resolved, with normalization of glucose, insulin, and C‐peptide levels and no signs of recurrence at follow‐up. Conclusion: This case highlights the clinical value of GLP‐1 receptor PET/CT for localizing insulinoma in the context of negative conventional or somatostatin receptor (SSTR)–based imaging. Accurate functional localization may directly guide minimally invasive therapeutic interventions and help avoid high‐risk reoperative pancreatic surgery.

Background/Objectives: Overactivation of the HGF/c-MET pathway is implicated in various cancers, making its inhibition a promising therapeutic strategy. While several MET-targeting agents are currently approved or in advanced clinical development, patient selection often relies on invasive tissue-based assays. The development of a specific c-MET radioligand for PET imaging and radioligand therapy represents a non-invasive alternative, enabling real-time monitoring of target expression and offering a pathway to personalized treatment. Methods: Radiosynthesis of [⁶⁸Ga]Ga-DOTA-EMP100 was performed using a GMP-certified ⁶⁸Ge/⁶⁸Ga generator connected to an automated synthesis module. The radiopharmaceutical production was optimized by scaling down the amount of DOTA-EMP-100 from 50 to 20 μg. Synthesis efficiency and release criteria were assessed according to Ph. Eur. for all the final products by evaluating radiochemical yield (RY%), radiochemical purity, presence of free gallium (by Radio-UV-HPLC) and gallium colloids (by Radio-TLC), molar activity (Am), chemical purity, pH, and LAL test results. Results: An optimized formulation of [⁶⁸Ga]Ga-DOTA-EMP-100, using 40 μg of precursor, provided the best outcome in terms of radiochemical performance. Process validation across three independent productions confirmed a consistent radiochemical yield of 64.5% ± 0.5, high radiochemical purity (>99.99%), and a molar activity of 53.41 GBq/µmol ± 0.8. Conclusions: [⁶⁸Ga]Ga-DOTA-EMP-100 was successfully synthesized with high purity and reproducibility, supporting its potential for multi-dose application in clinical PET imaging and targeted radioligand therapy.

Senescence is a dynamic, multifaceted process implicated in tissue aging, organ dysfunction, and intricately associated with numerous chronic diseases. As senescent cells accumulate, they drive inflammation, fibrosis, and metabolic disruption through the senescence-associated secretory phenotype (SASP). Despite its clinical relevance, senescence remains challenging to detect non-invasively due to its heterogeneous nature and the lack of universal biomarkers. Recent advances in the development of specific imaging probes for positron emission tomography (PET) enable in vivo visualization of senescence-associated pathways across key organs, such as the lung, heart, kidney, and metabolic processes. For instance, [¹⁸F]FPyGal, a β-galactosidase-targeted tracer, has demonstrated selective accumulation in senescent cells in both preclinical and early clinical studies, while FAP-targeted radioligands are emerging as tools for imaging fibrotic remodeling in the lung, liver, kidney, and myocardium. This review examines a new generation of PET radioligands targeting hallmark features of senescence, with the potential to track and measure the process, the ability to be translated into clinical interventions for early diagnosis, and longitudinal monitoring of senescence-driven pathologies. By integrating organ-specific imaging biomarkers with molecular insights, PET probes are poised to transform our ability to manage and treat age-related diseases through personalized approaches.