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

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 [¹²⁵I]I-R-(+)-7-chloro-8-hydroxy-1-(3′-iodopheny1)-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine ([¹²⁵I]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 [¹²⁵I]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, [¹²⁵I]I-R-(+)-TISCH showed specific binding signals to the pancreas. Furthermore, the uptakes of [¹²⁵I]I-R-(+)-TISCH in INS-1 cells were reduced in the presence of SCH23390 at different concentrations. [¹²⁵I]I-R-(+)-TISCH displayed a respectable uptake in insulinoma. Overall, [¹²⁵I]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.