Department of Radiology and Nuclear Medicine, Radboud university medical center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands,
Diabetologia. 2014 May;57(5):950-9. doi: 10.1007/s00125-014-3166-3. Epub 2014 Feb 1.
AIMS/HYPOTHESIS: A reliable method for in vivo quantification of pancreatic beta cell mass (BCM) could lead to further insight into the pathophysiology of diabetes. The glucagon-like peptide 1 receptor, abundantly expressed on beta cells, may be a suitable target for imaging. We investigated the potential of radiotracer imaging with the GLP-1 analogue exendin labelled with indium-111 for determination of BCM in vivo in a rodent model of beta cell loss and in patients with type 1 diabetes and healthy individuals.
The targeting of (111)In-labelled exendin was examined in a rat model of alloxan-induced beta cell loss. Rats were injected with 15 MBq (111)In-labelled exendin and single photon emission computed tomography (SPECT) acquisition was performed 1 h post injection, followed by dissection, biodistribution and ex vivo autoradiography studies of pancreatic sections. BCM was determined by morphometric analysis after staining with an anti-insulin antibody. For clinical evaluation SPECT was acquired 4, 24 and 48 h after injection of 150 MBq (111)In-labelled exendin in five patients with type 1 diabetes and five healthy individuals. The tracer uptake was determined by quantitative analysis of the SPECT images.
In rats, (111)In-labelled exendin specifically targets the beta cells and pancreatic uptake is highly correlated with BCM. In humans, the pancreas was visible in SPECT images and the pancreatic uptake showed high interindividual variation with a substantially lower uptake in patients with type 1 diabetes.
CONCLUSIONS/INTERPRETATION: These studies indicate that (111)In-labelled exendin may be suitable for non-invasive quantification of BCM.
ClinicalTrials.gov NCT01825148, EudraCT: 2012-000619-10.
目的/假设：一种可靠的活体定量胰腺β细胞质量（BCM）的方法可以进一步深入了解糖尿病的病理生理学。大量表达在β细胞上的胰高血糖素样肽 1 受体可能是成像的合适靶点。我们研究了用放射性示踪剂标记的 GLP-1 类似物 exendin 对体内β细胞丢失的啮齿动物模型和 1 型糖尿病患者和健康个体的 BCM 进行成像的潜力。
在胰岛细胞毒素诱导的β细胞丢失的大鼠模型中检查了（111）In 标记的 exendin 的靶向性。大鼠注射 15MBq（111）In 标记的 exendin，注射后 1 小时进行单光子发射计算机断层扫描（SPECT）采集，然后进行胰腺切片的生物分布和离体放射自显影研究。通过用抗胰岛素抗体染色后的形态计量分析确定 BCM。为了进行临床评估，在 5 例 1 型糖尿病患者和 5 例健康个体中，在注射 150MBq（111）In 标记的 exendin 后 4、24 和 48 小时进行 SPECT 采集。通过 SPECT 图像的定量分析确定示踪剂摄取。
在大鼠中，（111）In 标记的 exendin 特异性靶向β细胞，胰腺摄取与 BCM 高度相关。在人类中，SPECT 图像中可见胰腺，个体间的胰腺摄取差异很大，1 型糖尿病患者的摄取明显较低。
结论/解释：这些研究表明，（111）In 标记的 exendin 可能适合于 BCM 的非侵入性定量。
ClinicalTrials.gov NCT01825148，EudraCT：2012-000619-10。
