[125I](S)-trans-7-OH-PIPAT: a potential spect imaging agent for sigma binding sites

[125I](S)-trans-7-hydroxy-2-[(N-n-propyl-N-(3'-iodo-2'-propenyl)] aminotetralin ([125I](S)-trans-7-OH-PIPAT) has been prepared as an iodinated radioligand for studying the sigma binding site. [125I](S)-trans-7-OH-PIPAT binds to rat cerebellar membranes with a Kd = 1.67 +/- 0.07 nM and Bmax = 240 +/- 72 fmol/mg of protein (determined in the presence of 15 nM spiperone). This new ligand appears to bind to only one site with Hill coefficients close to unity. Inhibition constants for competing ligands determined in the cerebellar tissue homogenates (in the presence of 15 nM spiperone) are closely comparable to inhibition constants determined in the whole brain tissue homogenates (in the absence of spiperone). Furthermore, these inhibition constants are consistent with the values reported for typical sigma ligands. In vivo uptake of [125I](S)-trans-7-OH-PIPAT in the rat brain is initially high (2.52% dose/organ at 2 min post i.v. injection) and displays a rapid washout from the brain (0.8% dose/organ at 30 min post i.v. injection). Uptake of [125I](S)-trans-7-OH-PIPAT shows moderate target to non-target ratios at 30 minutes (1.54, 1.66 and 1.92 for cerebellar, hypothalamic and hindbrain uptake over striatal uptake, respectively). Pre-injection with haloperidol reduced these ratios to unity suggesting that the ligand binds specifically to haloperidol-sensitive sites in vivo. The selectivity and affinity of [125I](S)-trans-7-OH-PIPAT suggest that this new iodinated ligand may be useful for in vitro studies of the sigma sites and can be used in vivo as a potential SPECT imaging agent.