In vivo and in vitro binding of [I-125]I-R-(+)-TISCH: A dopamine D-1 receptor ligand for studying pancreatic beta-cell mass

Diabetes mellitus (DM) and insulinoma are mainly affected by the status of pancreatic beta-cell mass (BCM). Development of imaging agents for BCM allows to study pancreatic beta cells and the relationship between beta cells and DM or insulinoma. In this study, we investigated the density of dopamine D-1 receptor on the beta cells and measured BCM by statistical image processing. The pancreatic uptakes of [I-125]I-R-(+)-7-chloro-8-hydroxy-1-(3'-iodopheny1)-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine ([I-125]I-R-(+)-TISCH), dopamine D-1 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 [I-125]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, [I-125]I-R-(+)-TISCH showed specific binding signals to the pancreas. Furthermore, the uptakes of [I-125]I-R-(+)-TISCH in INS-1 cells were reduced in the presence of SCH23390 at different concentrations. [I-125]I-R-(+)-TISCH displayed a respectable uptake in insulinoma. Overall, [I-125]I-R-(+)-TISCH provided specific binding signals to pancreatic beta cells. Although the specific signal may not be sufficient for imaging in vivo, the dopamine D-1 receptor can still be considered as a potential target for studying BCM. Further investigation will be required to optimize the ligand.