A non-invasive method of pancreatic β-cell mass measurement is needed to enhance our understanding of the pathogenesis of diabetes, facilitate the early diagnosis of this disease, and promote the development of novel therapeutics. Here, we described the synthesis of a novel indium-111 (¹¹¹In) exendin-4 derivative, [Lys¹²(In-BnDTPA-Ahx)]exendin-4, through a process involving isothiocyanate-benzyl-DTPA (BnDTPA) and 6-aminohexanoic acid (Ahx) attached to an ɛ-amino group at the lysine-12 residue. We further evaluated the potential use of this derivative as a SPECT probe for pancreatic β-cell imaging. An in vitro binding assay revealed that [Lys¹²(^natIn-BnDTPA-Ahx)]exendin-4 has a high affinity for GLP-1 receptors (IC₅₀ = 0.43 nM). In biodistribution experiments involving normal mice, high [Lys¹²(¹¹¹In-BnDTPA-Ahx)]exendin-4 uptake was observed in the pancreas (21.8 ± 4.0 %ID/g) and was maintained for 2 h after injection. Pre-injection of excess exendin(9−39) markedly reduced the pancreatic uptake of [Lys¹²(¹¹¹In-BnDTPA-Ahx)]exendin-4 (95.2%), indicating that the uptake of this tracer is specific and mediated by GLP-1 receptors. Ex vivo autoradiography experiments involving pancreatic sections from MIP-GFP mice confirmed the accumulation of [Lys¹²(¹¹¹In-BnDTPA-Ahx)]exendin-4 in pancreatic β-cells. Finally, in mice, [Lys¹²(¹¹¹In-BnDTPA-Ahx)]exendin-4 SPECT/CT yielded clear images of the pancreas at 30 min post-injection. In conclusion, SPECT with [Lys¹²(¹¹¹In-BnDTPA-Ahx)]exendin-4 enables to visualize β-cells in vivo non-invasively.

需要一种非侵入性的胰腺β细胞质量测量方法，以增强我们对糖尿病发病机制的了解，促进这种疾病的早期诊断并促进新型疗法的发展。在这里，我们描述了通过涉及异硫氰酸酯-苄基-DTPA（BnDTPA）和6的过程合成新型铟111（¹¹¹ In）exendin-4衍生物[Lys ¹²（In-BnDTPA-Ahx）] exendin-4的方法。 -在赖氨酸-12残基的α-氨基上连接的-氨基己酸（Ahx）。我们进一步评估了该衍生物作为SPECT探针用于胰腺β细胞成像的潜在用途。的体外结合测定显示，[赖氨酸¹²（^NATIn-BnDTPA-Ahx）exendin-4对GLP-1受体具有很高的亲和力（IC ₅₀  = 0.43 nM）。在涉及正常小鼠的生物分布实验中，在胰腺中观察到了高[Lys ¹²（¹¹¹ In-BnDTPA-Ahx）] exendin-4摄取（21.8±4.0％ID / g），并在注射后维持2 h。预注射过量的exendin（9-39）显着降低了[Lys ¹²（¹¹¹ In-BnDTPA-Ahx）] exendin-4（95.2％）的胰腺摄取，表明该示踪剂的摄取是特异性的，并由GLP介导-1受体。涉及MIP-GFP小鼠胰腺切片的离体放射自显影实验证实了[Lys ¹²（¹¹¹In-BnDTPA-Ahx）] exendin-4在胰腺β细胞中。最后，在小鼠中，[Lys ¹²（¹¹¹ In-BnDTPA-Ahx）] exendin-4 SPECT / CT在注射后30分钟时产生了清晰的胰腺图像。总之，具有[Lys ¹²（¹¹¹ In-BnDTPA-Ahx）] exendin-4的SPECT能够非侵入性地可视化体内的β细胞。