Purpose: [68Ga]Ga-DOTA-peptide uptake in the pancreatic head/uncinate process (UP) is a frequent PET/CT finding. Although mostly physiologic, it can represent a pitfall in PET/CT reading, especially when focal. An increased frequency of UP uptake has been reported in patients (pts) affected by diabetes mellitus (DM). The aim of the study is to describe the frequency of [68Ga]Ga-DOTANOC UP uptake to evaluate its variations over time and its possible correlation with DM. Methods: In September 2017, a monocentric prospective observational electronic archive was initiated at our center to collect clinical and imaging data of pts undergoing [68Ga]Ga-DOTANOC PET/CT. Among the pts enrolled in the first 6 months (Sept 2017 to Feb 2018), those presenting [68Ga]Ga-DOTANOC PET/CT uptake at UP level were included. Pts with UP lesions already documented on CT/MRI or those that underwent surgical excision of UP before PET/CT were excluded from the analysis. [68Ga]Ga-DOTANOC UP uptake was classified as diffuse or focal and compared with the pattern observed in previous PET/CT scans performed at our center. An increased frequency of UP uptake was also correlated with the presence of DM. Results: In the first 6 months, 253 pts were enrolled in the archive and 172 out of them were included in the analysis. UP increased uptake was frequently observed (77/172, 44.8%) and was mostly diffuse (62/77). In 75/172 pts (43.6%), previous [68Ga]Ga-DOTANOC PET/CT scans were available (overall 268 scans; number of previous PET per pt range: 1–20) and were retrospectively reviewed. Despite the fact that, in most pts, the uptake pattern was stable over time (54/75 pts, 72%), it changed in approximately one third of cases (21/75, 28%). Among DM pts (29/172), only 10/29 (34.4%) presented increased UP uptake. Conclusions: UP [68Ga]Ga-DOTANOC uptake is a frequent non-malignant finding (slightly higher than previously reported), mostly presenting with a diffuse pattern. However, contrary to previous reports, our data show that the pattern of uptake may vary over time in approximately one third of the cases and it is not more frequently observed in pts with DM.
Pancreatic neuroendocrine neoplasms (panNENs) are heterogeneous neoplasms with neuroendocrine differentiation that show peculiar clinical and histomorphological features, with variable prognosis. In recent years, advances in knowledge regarding the pathophysiology and heterogeneous clinical presentation, as well as the availability of different diagnostic procedures for panNEN diagnosis and novel therapeutic options for patient clinical management, has led to the recognition of the need for an active multidisciplinary discussion for optimal patient care. Molecular imaging with positron emission tomography/computed tomography (PET/CT) has become indispensable for the management of panNENs. Several PET radiopharmaceuticals can be used to characterize either panNEN receptor expression or metabolism. The aim of this review is to offer an overview of all the currently used radiopharmaceuticals and of the new upcoming tracers for pancreatic neuroendocrine tumors (panNETs), and their clinical impact on therapy management. [68Ga]Ga-DOTA-peptide PET/CT (SSA-PET/CT) has high sensitivity, specificity, and accuracy and is recommended for the staging and restaging of any non-insulinoma well-differentiated panNEN cases to carry out detection of unknown primary tumor sites or early relapse and for evaluation of in vivo somatostatin receptors expression (SRE) to select patient candidates for peptide receptor radiometabolic treatment (PRRT) with 90Y or 177Lu and/or cold analogs. SSA-PET/CT also has a strong impact on clinical management, leading to a change in treatment in approximately a third of the cases. Its role for treatment response assessment is still under debate due to the lack of standardized criteria, even though some semiquantitative parameters seem to be able to predict response. [18F]FDG PET/CT generally shows low sensitivity in small growing and well-differentiated neuroendocrine tumors (NET; G1 and G2), while it is of utmost importance in the evaluation and management of high-grade NENs and also provides important prognostic information. When positive, [18F]FDG PET/CT impacts therapeutical management, indicating the need for a more aggressive treatment regime. Although FDG positivity does not exclude the patient from PRRT, several studies have demonstrated that it is certainly useful to predict response, even in this setting. The role of [18F]FDOPA for the study of panNET is limited by physiological uptake in the pancreas and is therefore not recommended. Moreover, it provides no information on SRE that has crucial clinical management relevance. Early acquisition of the abdomen and premedication with carbidopa may be useful to increase the accuracy, but further studies are needed to clarify its utility. GLP-1R agonists, such as exendin-4, are particularly useful for benign insulinoma detection, but their accuracy decreases in the case of malignant insulinomas. Being a whole-body imaging technique, exendin-PET/CT gives important preoperative information on tumor size and localization, which is fundamental for surgical planning as resection (enucleation of the lesion or partial pancreatic resection) is the only curative treatment. New upcoming tracers are under study, such as promising SSTR antagonists, which show a favorable biodistribution and higher tumor-to-background ratio that increases tumor detection, especially in the liver. [68Ga]pentixafor, an in vivo marker of CXCR4 expression associated with the behavior of more aggressive tumors, seems to only play a limited role in detecting well-differentiated NET since there is an inverse expression of SSTR2 and CXCR4 in G1 to G3 NETs with an elevation in CXCR4 and a decrease in SSTR2 expression with increasing grade. Other tracers, such as [68Ga]Ga-PSMA, [68Ga]Ga-DATA-TOC, [18F]SiTATE, and [18F]AlF-OC, are also under investigation.
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