Brom Maarten, Joosten Lieke, Frielink Cathelijne, Boerman Otto, Gotthardt Martin
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
Diabetes. 2015 Apr;64(4):1324-8. doi: 10.2337/db14-1212. Epub 2014 Nov 19.
Targeting of the GLP-1 receptor with (111)In-labeled exendin is an attractive approach to determine the β-cell mass (BCM). Preclinical studies as well as a proof-of-concept study in type 1 diabetic patients and healthy subjects showed a direct correlation between BCM and radiotracer uptake. Despite these promising initial results, the influence of α-cells on the uptake of the radiotracer remains a matter of debate. In this study, we determined the correlation between pancreatic tracer uptake and β- and α-cell mass in a rat model for β-cell loss. The uptake of (111)In-exendin (% ID/g) showed a strong positive linear correlation with the BCM (Pearson r = 0.82). The fraction of glucagon-positive cells in the total endocrine mass was increased after alloxan treatment (26% ± 4%, 43% ± 8%, and 69% ± 21% for 0, 45, and 60 mg/kg alloxan, respectively). The uptake of (111)In-exendin showed a negative linear correlation with the α-cell fraction (Pearson r = -0.76). These data clearly indicate toward specificity of (111)In-exendin for β-cells and that the influence of the α-cells on (111)In-exendin uptake is negligible.
用（111）铟标记的艾塞那肽靶向胰高血糖素样肽-1（GLP-1）受体是一种测定β细胞量（BCM）的有吸引力的方法。临床前研究以及一项针对1型糖尿病患者和健康受试者的概念验证研究表明，BCM与放射性示踪剂摄取之间存在直接相关性。尽管有这些令人鼓舞的初步结果，但α细胞对放射性示踪剂摄取的影响仍存在争议。在本研究中，我们在一个β细胞缺失的大鼠模型中确定了胰腺示踪剂摄取与β细胞和α细胞量之间的相关性。（111）铟-艾塞那肽的摄取（%ID/g）与BCM呈强正线性相关（Pearson相关系数r = 0.82）。用四氧嘧啶处理后，胰高血糖素阳性细胞在总内分泌细胞量中的比例增加（分别给予0、45和60 mg/kg四氧嘧啶时，比例分别为26%±4%、43%±8%和69%±21%）。（111）铟-艾塞那肽的摄取与α细胞比例呈负线性相关（Pearson相关系数r = -0.76）。这些数据清楚地表明（111）铟-艾塞那肽对β细胞具有特异性，且α细胞对（111）铟-艾塞那肽摄取的影响可忽略不计。
