Preclinical PET Platform (O.E., I.V., R.K.S.), Department of Medicinal Chemistry, Uppsala University, SE-751 83 Uppsala, Sweden; Department of Radiology, Oncology, and Radiation Sciences (I.V., L.J., G.A., J.S.), Uppsala University, SE-751 83 Uppsala, Sweden; PET Centre (I.V., G.A., J.S.), Centre for Medical Imaging, Uppsala University Hospital, Uppsala, SE-751 83 Sweden; Beckman Research Institute of the City of Hope (F.K.), Duarte, California 91010; AstraZeneca R&D (L.J.), SE-431 50 Mölndal, Sweden; Department of Medical Sciences (B.E.), Uppsala University, SE-751 83 Uppsala, Sweden; and Department of Immunology, Genetics, and Pathology (O.K.), Uppsala University SE-751 83, Uppsala, Sweden.
J Clin Endocrinol Metab. 2014 May;99(5):1519-24. doi: 10.1210/jc.2013-3541. Epub 2014 Feb 10.
Insulinomas are the most common cause of endogenous hyperinsulinemic hypoglycemia in nondiabetic adult patients. They are usually benign, and curative surgery is the "gold standard" treatment if they can be localized. Malignant insulinomas are seen in less than 10% of patients, and their prognosis is poor. The glucagon like peptide-1 receptor (GLP-1R) is markedly up-regulated in insulinomas-especially benign lesions, which are difficult to localize with current imaging techniques.
The aim of the study was to assess the possibility of the detection of primary and metastatic insulinoma by positron emission tomography (PET) using [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 ([(68)Ga]Exendin-4) in a patient with severe hypoglycemia.
Dynamic and static PET/computed tomography (CT) examination of a patient was performed using [(68)Ga]Exendin-4 at Uppsala University Hospital, Uppsala, Sweden.
A patient presented with hypoglycemia requiring continuous iv glucose infusions. A pancreatic insulinoma was suspected, and an exploratory laparotomy was urgently performed. At surgery, a tumor in the pancreatic tail with an adjacent metastasis was found, and a distal pancreatic resection (plus splenectomy) and removal of lymph node were performed. Histopathology showed a World Health Organization classification grade II insulinoma. Postoperatively, hypoglycemia persisted, but a PET/CT examination using the neuroendocrine marker [(11)C]-5-hydroxy-L-tryptophan was negative.
The patient was administered [(68)Ga]Exendin-4 and was examined by dynamic PET over the liver and pancreas.
The stable GLP-1 analog Exendin-4 was labeled with (68)Ga for PET imaging of GLP-1R-expressing tumors. The patient was examined by [(68)Ga]Exendin-4-PET/CT, which confirmed several small GLP-1R-positive lesions in the liver and a lymph node that could not be conclusively identified by other imaging techniques. The results obtained from the [(68)Ga]Exendin-4-PET/CT examination provided the basis for continued systemic treatment.
The results of the [(68)Ga]Exendin-4-PET/CT examination governed the treatment strategy of this particular patient and demonstrated the potential of this technique for future management of patients with this rare but potentially fatal disease.
在非糖尿病成年患者中，胰岛素瘤是内源性高胰岛素血症低血糖的最常见原因。它们通常是良性的，如果能够定位，手术治疗是“金标准”。不到 10%的患者可见恶性胰岛素瘤，其预后较差。在胰岛素瘤中，胰高血糖素样肽-1 受体（GLP-1R）明显上调-特别是良性病变，目前的影像学技术难以定位。
本研究旨在评估使用正电子发射断层扫描（PET）用 [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4([(68)Ga]Exendin-4) 检测原发性和转移性胰岛素瘤的可能性，该患者患有严重低血糖。
在瑞典乌普萨拉大学医院对患者进行 [(68)Ga]Exendin-4 的动态和静态 PET/计算机断层扫描（CT）检查。
一名患者出现低血糖，需要持续静脉输注葡萄糖。怀疑胰腺胰岛素瘤，紧急行剖腹探查术。术中发现胰尾肿瘤伴邻近转移，行胰尾切除术（加脾切除术）和淋巴结切除。组织病理学显示世界卫生组织分级 II 级胰岛素瘤。术后，低血糖持续存在，但神经内分泌标志物 [(11)C]-5-羟色氨酸的 PET/CT 检查为阴性。
给患者注射 [(68)Ga]Exendin-4 并进行肝胰动态 PET 检查。
稳定的 GLP-1 类似物 Exendin-4 用 (68)Ga 标记用于 GLP-1R 表达肿瘤的 PET 成像。对患者进行 [(68)Ga]Exendin-4-PET/CT 检查，证实肝脏中有几个较小的 GLP-1R 阳性病变和一个不能通过其他影像学技术明确识别的淋巴结。[(68)Ga]Exendin-4-PET/CT 检查结果为进一步的全身治疗提供了依据。
[(68)Ga]Exendin-4-PET/CT 检查结果指导了该特定患者的治疗策略，并证明了该技术在未来管理这种罕见但可能致命疾病患者中的潜力。
