Brain serotonin systems are implicated in psychiatric disorders, including depression, anxiety and schizophrenia. At least 14 subtypes of serotonin receptors have been identified by cloning techniques. Of these, the serotonin 5-HT1A receptor has been identified as the direct target of atypical anxiolytic drugs such as buspirone and the indirect target of antidepressant drugs. The primary objective of this project is to develop imaging agents to monitor the 5-HT1A receptor in living brain with SPECT. The most widely used radionuclide in nuclear medicine is 99mtechnetium (99mTc; T+ 6hr) because it can be generated in a laboratory from a kit. As an initial step in development, rhenium analogs of the final target technetium compounds are tested in vitro. The 5-HT1A receptor was detected in frontal cortex of rhesus monkey brain with the 5-HT1A receptor ligand [3H]-8-OH-DPAT (0.6 nM), incubated in the presence of clonidine and prazosin to mask other potential targets of the radioligand. Nonspecific binding was measured with buspirone (3 fM) or serotonin (10 fM). Pilot studies were conducted to determine whether two 5-HT1A receptor ligands, coupled to a rhenium chelate would retain high affinity binding to the 5-HT1A serotonin receptor. REO-1 displayed relatively high affinity for the 5-HT1A receptor (IC50 30 nM) whereas REO-2 was of lower affinity (IC50 200 nM). These studies indicate the feasibility of developing rhenium chelate analogs
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