In vivo characteristics of IBZM in rat brains: An agent for quantitative SPECT imaging of dopamine D₂ receptors. Preparation of ¹²⁵I-IBZM and its biodistribution and kinetic properties

¹²³I-(S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1 ethyl-2-pyrrolidinyl)methyl]-benzamide (IBZM) is a CNS dopamine D₂ receptor imaging agent for SPECT and has already been used clinically in the United States, Canada and Europe. However, methods of quantitative SPECT measurement of the D₂ receptor density have not been well established. We performed in vivo biodistribution studies of ¹²⁵I-IBZM in rat brains as the first step toward establishment of a basis for quantitative SPECT imaging of D₂ receptors in humans. ¹²⁵I-IBZM was prepared by the chloramine-T method. Radiochemical yields were 80 to 90% and radiochemical purity was 94.7% on day 81 after labeling. At 10, 30, 60 and 120 min after injection of the radiopharmaceutical, the percent uptakes (% dose/g) in the rat striatum were 2.9, 1.9, 1.7 and 1.0, respectively. These kinetic data were considered suitable for SPECT imagings. Pretreatment with haloperidol (1 mg/kg) blocked specific striatal uptake and there was a significant reduction in the uptake to 40.9% of the unblocked uptake at 60 min after injection (p = 0.006). The regional IBZM uptake ratio of striatum-to-cerebellum increased steadily from 1.7 at 10 min to 5.7 at 120 min. This suggests that SPECT imaging must be done during fixed time after tracer injection for the semiquantitative ratio to be meaningful.