Validation of radiolabelled exendin for beta cell imaging by ex vivo autoradiography and immunohistochemistry of human pancreas.

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-10-15 DOI:10.1186/s13550-024-01159-6

Theodorus J P Jansen, Sevilay Tokgöz, Mijke Buitinga, Sanne A M van Lith, Lieke Joosten, Cathelijne Frielink, Esther M M Smeets, Martijn W J Stommel, Marion B van der Kolk, Bastiaan E de Galan, Maarten Brom, Marti Boss, Martin Gotthardt

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Abstract

Background: Estimation of beta cell mass is currently restricted to evaluating pancreatic tissue samples, which provides limited information. A non-invasive imaging technique that reliably quantifies beta cell mass enables monitoring of changes of beta cell mass during the progression of diabetes mellitus and may contribute to monitoring of therapy effectiveness. We assessed the specificity of radiolabelled exendin for beta cell mass quantification in humans. Fourteen adults with pancreas tumours were injected with ¹¹¹In-labeled exendin-4 prior to pancreatic resection. In resected pancreas tissue, endocrine-exocrine ratios of tracer uptake were determined by digital autoradiography and accumulation of ¹¹¹In-labeled exendin-4 was compared to insulin and GLP-1 receptor staining. Of four participants, abdominal single photon emission computed tomography/computed tomography (SPECT/CT) images were acquired to quantify pancreatic uptake in vivo RESULTS: Tracer uptake was predominantly present in the endocrine pancreas (endocrine-exocrine ratio: 3.6 [2.8-10.8]. Tracer accumulation showed overlap with insulin-positive regions, which overlapped with GLP-1 receptor positive areas. SPECT imaging showed pancreatic uptake of radiolabelled exendin in three participants.

Conclusion: Radiolabelled exendin specifically accumulates in the islets of Langerhans in human pancreas tissue. The clear overlap between regions positive for insulin and the GLP-1 receptor substantiate the beta cell specificity of the tracer. Radiolabelled exendin is therefore a valuable imaging agent for human beta cell mass quantification and has the potential to be used for a range of applications, including improvement of diabetes treatment by assessment of the effects of current and novel diabetes therapies on the beta cell mass.

Trial registration: ClinicalTrials.gov NCT03889496, registered 26,032,019, URL https://clinicaltrials.gov/study/NCT03889496?term=NCT03889496 .

Clinicaltrials: gov NCT04733508, registered 02022021, URL https://clinicaltrials.gov/study/NCT04733508 .

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通过人体胰腺体外自显影和免疫组化技术验证用于β细胞成像的放射性标记外显素。

背景：目前，对β细胞质量的估计仅限于对胰腺组织样本进行评估，这只能提供有限的信息。一种能可靠量化β细胞质量的无创成像技术能监测糖尿病进展过程中β细胞质量的变化，并有助于监测治疗效果。我们评估了放射性标记的 exendin 对人体 beta 细胞质量量化的特异性。14名患有胰腺肿瘤的成年人在胰腺切除术前注射了111In标记的外显素-4。在切除的胰腺组织中，通过数字自显影测定示踪剂摄取的内分泌-外分泌比率，并将111In标记的外显素-4的积累与胰岛素和GLP-1受体染色进行比较。结果：示踪剂摄取主要存在于胰腺内分泌部位（内分泌-外分泌比率：3.6 [2.8-10.8]）。示踪剂累积显示与胰岛素阳性区域重叠，而胰岛素阳性区域又与 GLP-1 受体阳性区域重叠。SPECT 成像显示，三名参与者的胰腺摄取了放射性标记的依那西汀：结论：放射性标记的 exendin 会特异性地聚集在人体胰腺组织中的朗格汉斯胰岛。胰岛素和 GLP-1 受体阳性区域的明显重叠证实了示踪剂的β细胞特异性。因此，放射性标记的 exendin 是一种有价值的成像剂，可用于人体 beta 细胞质量的量化，并有可能用于一系列应用，包括通过评估当前和新型糖尿病疗法对 beta 细胞质量的影响来改进糖尿病治疗：ClinicalTrials.gov NCT03889496，注册号 26,032,019，网址 https://clinicaltrials.gov/study/NCT03889496?term=NCT03889496 .Clinicaltrials: gov NCT04733508，注册号 02022021，网址 https://clinicaltrials.gov/study/NCT04733508 。

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