In vivo and in vitro binding of [125I]I‐R‐(+)‐TISCH: A dopamine D1 receptor ligand for studying pancreatic β‐cell mass. (6th November 2022)

• Record Type: Journal Article
• Authors: Zhang, Yan; Li, Guangwen; Sun, Yuli; Hong, Haiyan; Li, Linlin; Luo, Yang; Wang, Ran; Zhu, Lin; Kung, Hank F.; Zhu, Jinxia
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 65:Number 14(2022)
• Page Start: 354
• Page End: 360
• Publication Date: 2022-11-06
• Subjects: [125I]I‐R‐(+)‐TISCH -- dopamine D1 receptor -- pancreas -- β‐Cell mass; Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.4005
• Languages: English
• ISSNs: 0362-4803

Abstract

Abstract : Diabetes mellitus (DM) and insulinoma are mainly affected by the status of pancreatic β‐cell mass (BCM). Development of imaging agents for BCM allows to study pancreatic β cells and the relationship between β cells and DM or insulinoma. In this study, we investigated the density of dopamine D1 receptor on the β cells and measured BCM by statistical image processing. The pancreatic uptakes of [ 125 I]I‐R‐(+)‐7‐chloro‐8‐hydroxy‐1‐(3′‐iodopheny1)‐3‐methyl‐2, 3, 4, 5‐tetrahydro‐1H‐3‐benzazepine ([ 125 I]I‐R‐(+)‐TISCH), dopamine D1 receptor tracer, in normal and diabetic rats displayed significant differences at 30 min (1.11 ± 0.08% ID/g vs. 0.63 ± 0.09% ID/g, p < 0.0001). In the presence of SCH23390, the pancreatic uptake of [ 125 I]I‐R‐(+)‐TISCH at 30 min in normal rats was lower (1.01 ± 0.04% ID/g, p < 0.05). Although the blocking was not complete, [ 125 I]I‐R‐(+)‐TISCH showed specific binding signals to the pancreas. Furthermore, the uptakes of [ 125 I]I‐R‐(+)‐TISCH in INS‐1 cells were reduced in the presence of SCH23390 at different concentrations. [ 125 I]I‐R‐(+)‐TISCH displayed a respectable uptake in insulinoma. Overall, [ 125 I]I‐R‐(+)‐TISCH provided specific binding signals to pancreatic β cells. Although the specific signal may not be sufficient for imaging in vivo, the dopamine D1 receptor can still be considered as a potential target for studying BCM. Further investigation will be required to optimize the ligand. Abstract : A dopamine D1 receptor‐targeted tracer, [ 125 I]I‐R‐(+)‐TISCH, provided a moderate specific binding signal to pancreatic β cells in rats. The dopamine D1 receptor may serve as a promising target for studying insulinoma and measuring β‐cell mass (BCM).