The biodistribution and dosimetry of FIDA-2: A D2 dopamine receptor antagonist for use with both PET and SPECT

FIDA-2 (R-(+)-2,3-dimethoxy-5-iodo-N-[(1-4`-fluorobenzyl)-2-pyrrolidinyl) methyl] benzamide is a simultaneously fluorinated and iodinated D2/D3 dopamine receptor antagonist that can be labeled with either F-18 or I-123 without changing the biological properties of the ligand. In vitro binding studies in Sf9 cell lines have shown that it has a Kd for the D2 receptor of 0.04 nM, and a Kd for the D3 receptor of 0.05 nM. The purpose of this study was to measure its biodistribution and radiation safety in healthy humans. The dosimetry was measured with 100-150 MBq (2.7-3.6 mCi) of the I-123 labeled product in 3 men and 3 women with a mean age of 30.2 years (range: 23-43). Transmission scans were made with a sheet source containing about 200 MBq of I-123. Up to 7 whole body scans were aquired for 24 to 27 hours after administration on a dual headed camera. Regions of interest were placed on the initial images and transposed as a single set onto all the other scans. The geometric organ means were corrected for decay and attenuation and compared to the net counts in the injected dose. The renal excretion fraction was measured by collecting all the urine that was voided for the first 16more » hours after injection. Biexponential functions were fit to the time activity curves for each organ and integrated to calculate the residence times for the F-18 and I-123 labeled ligands. There were no subjective effects of the tracer on any of the subjects. The vital signs remained stable, and the clinical laboratory studies that were performed on serum samples before and after the procedure did not change significantly. The data suggest that high resolution images of the brain can be safely acquired with 185 MBq (5 mCi) of I-123 or F-18 FIDA-2.« less