Heterogeneity of Multiple Pancreatic Neuroendocrine Tumors Identified by 68Ga-DOTANOC and 68Ga-Exendin-4 PET/CT in a Patient with Endogenous Hyperinsulinemic Hypoglycemia and Multiple Endocrine Neoplasia 1.

INTRODUCTION: Insulinomas are the most frequent functional pancreatic neuroendocrine tumors. In about 10% of cases, insulinomas are associated with hereditary syndromes, including multiple endocrine neoplasia 1 (MEN1). CASE PRESENTATION: Herein, we present a 44-year-old female with recurrent hypoglycemia. In December 1998, this patient underwent resection of two pancreatic lesions due to hypoglycemia and was diagnosed with insulinoma. After the operation, the symptoms of hypoglycemia disappeared. However, from 2021, hypoglycemic symptoms reappeared frequently, as did coma. In June 2023, enhanced CT showed multiple pancreatic lesions abundant with blood supply. Fasting serum blood glucose and insulin were 1.73 mmol/L and 15.2 U/L (2.6-11.8 U/L). Germline genes suggested MEN1 pathogenic mutations. 68Ga-DOTANOC PET/CT indicated there were multiple lesions located in the pancreas and duodenum with high expression of the somatostatin receptor (SSTR). 68Ga-exendin-4 PET/CT was added to localize the insulinoma. Most lesions with high expression of SSTR in the body and tail of the pancreas manifested parts of them with high uptake of 68Ga-exendin-4, and an additional lesion with high expression of glucagon-like peptide-1 receptor (GLP-1R) was only detected by 68Ga-exendin-4 PET/CT. It showed inter-tumor heterogeneity in the expression of SSTR and GLP-1R. From the distal pancreatectomy, a total of 5 tumors were found in the body and tail of the pancreas, which were diagnosed as neuroendocrine tumors (NETs). After the operation, all the symptoms related to hypoglycemia disappeared. Immunohistochemical results of SSTR2 and insulin were consistent with the imaging findings of dual-tracer PET/CT. CONCLUSION: From this case, a combination of 68Ga-DOTANOC and 68Ga-exendin-4 PET/CT was recommended in the patients with MEN1 and insulinoma to estimate the heterogeneity of multiple neuroendocrine tumors that contribute to detect all the NET lesions and locate the tumors with secretion of insulin.

Ectopic insulinoma: case report.

BACKGROUND: Ectopic insulinoma is a rare entity that is difficult to diagnose before surgery. This article reports two cases of ectopic insulinoma. CASE PRESENTATION: Two patients manifested recurrent hypoglycemia with a typical Whipple triad. In terms of the qualitative diagnosis, the oral glucose tolerance test (OGTT) suggested a diagnosis of hyperinsulinemic hypoglycemia. However, preoperative imaging did not show a significant mass in the pancreas. In one patient, preoperative abdominal enhanced volume perfusion computed tomography (CT), somatostatin receptor imaging and 99mTc-HYNIC-TOC SPECT/CT revealed a mass with a rich blood supply anterior to the duodenum. In the other patient, preoperative enhanced CT, magnetic resonance imaging (MRI) and 68Ga-Exendin-4 PET/CT showed a mass above the spleen. After surgical removal of the tumor, both patients received a confirmed diagnosis of neuroendocrine tumors by postoperative pathology. The symptoms of hypoglycemia were relieved after surgery, and the blood glucose level was significantly increased. CONCLUSION: Ectopic insulinoma is difficult to locate before surgery. 68Ga-Exendin-4 PET/CT has a high diagnostic value. Surgical removal of the lesion is main treatment.

Nuclear Medicine and Radiological Imaging of Pancreatic Neuroendocrine Neoplasms: A Multidisciplinary Update.

Pancreatic neuroendocrine neoplasms (panNENs) are part of a large family of tumors arising from the neuroendocrine system. PanNENs show low-intermediate tumor grade and generally high somatostatin receptor (SSTR) expression. Therefore, panNENs benefit from functional imaging with 68Ga-somatostatin analogues (SSA) for diagnosis, staging, and treatment choice in parallel with morphological imaging. This narrative review aims to present conventional imaging techniques and new perspectives in the management of panNENs, providing the clinicians with useful insight for clinical practice. The 68Ga-SSA PET/CT is the most widely used in panNENs, not only fr diagnosis and staging purpose but also to characterize the biology of the tumor and its responsiveness to SSAs. On the contrary, the 18F-Fluordeoxiglucose (FDG) PET/CT is not employed systematically in all panNEN patients, being generally preferred in G2-G3, to predict aggressiveness and progression rate. The combination of 68Ga-SSA PET/CT and 18F-FDG PET/CT can finally suggest the best therapeutic strategy. Other radiopharmaceuticals are 68Ga-exendin-4 in case of insulinomas and 18F-dopamine (DOPA), which can be helpful in SSTR-negative tumors. New promising but still-under-investigation radiopharmaceuticals include radiolabeled SSTR antagonists and 18F-SSAs. Conventional imaging includes contrast enhanced CT and multiparametric MRI. There are now enriched by radiomics, a new non-invasive imaging approach, very promising to early predict tumor response or progression.

Radioguided Surgery in Insulinoma Using 68Ga Labeled Exendin-4: a Case Report.

Laparoscopic resection of tumor is often performed for benign and small insulinomas, or for those located in the body or tail of the pancreas. The precise preoperative and intraoperative localization of the insulinoma is critical to minimize the surgical intervention. Conventional imaging studies, i.e., MRI, CT, and endoscopic ultrasound have limited sensitivity due to the small size of the insulinomas. Angiography, intraarterial calcium stimulation, and venous sampling are invasive procedures with concomitant risk for complications. Exendin-4 PET/CT scan has shown to be of great value in preoperative localization of insulinomas. In the absence of the traditional gold standard, i.e., intraoperative ultrasound with manual palpation, in laparoscopic surgery, a simple enucleation procedure might not be possible. Gamma probe-assisted surgery is a new method of diagnosis and treatment which allows a small area of tissue to be identified and removed, while a large area of the organ or the system remains unaffected. We present a case of a 34-year-old man with clinical suspicion of insulinoma with negative conventional imaging and successful lesion localization with 68Ga-Exendin-4 PET/CT scan in the pancreatic body, who underwent laparoscopic enucleation of the lesion with the aid of a hand-held gamma detecting probe.

Extrapancreatic insulinoma.

A 38-year-old female presented with recurrent episodes of hypoglycemia for 5 years. On 72-h fast test, critical sample biochemistry was suggestive of endogenous hyperinsulinemic hypoglycemia. Both constrast-enhanced computed tomography and 68Ga-DOTATATE positron emission tomography/computerized tomography (PET/CT) revealed no pancreatic lesion but showed a jejunal lesion suggestive of neuroendocrine tumor (NET) but not confirmatory of insulinoma. 68Ga-Exendin-4 PET/CT showed intense uptake in the proximal jejunum, and this being a specific scan for insulinoma, confirmed it as an ectopic insulinoma. The patient attained normoglycemia after excision of this NET confirming it to be a case of ectopic insulinoma located in the jejunum. Although most insulinomas are located in the pancreas, rarely ectopic cases have been described in the spleen, perisplenic tissue, duodenohepatic ligament, adjacent to the ligament of Treitz, duodenum, and the jejunum. Functional scanning with 68Ga-Exendin-4 PET/CT scan aids the localization of ectopic insulinoma.

Rare malignant insulinoma with multiple liver metastases derived from ectopic pancreas: 3-year follow-up and literature review.

Here, we report the diagnosis and treatment of a very rare case of malignant insulinoma derived from ectopic pancreas. A middle-aged woman presented with a 6-year history of recurrent hypoglycemia with multiple lesions in liver. Admission workup revealed elevated serum insulin and C-peptide, as well as multiple lesions in the liver (largest being 4.3 cm), enlarged lymph nodes around the pancreas, and a lesion (of 3.5 cm) at the proximal jejunum, as shown by contrast computed tomography (CT). Liver biopsy showed the lesions to be well-differentiated neuroendocrine tumors, grade G1. 68Gallium-exendin-4 positron emission tomography/CT confirmed the origin as the lesion located at the jejunum. The combination treatment of everolimus plus long-acting octreotide relieved symptoms and achieved a partial tumor response. Maintenance treatment of the somatostatin analog (ie, octreotide) alone was administered. Three years of follow-up, up to the writing of this report, showed good survival, with the patient remaining asymptomatic and euglycemic without disease progression. This case shows that 68Gallium-exendin-4 positron emission tomography/CT is useful for locating insulinoma, especially for insulinoma derived from ectopic pancreas, and that everolimus plus octreotide with maintenance somatostatin analog alone is an effective drug strategy for treating inoperable malignant insulinoma.