Preparation and evaluation of 3-[125I]iodo-4-aminophentermine as a brain perfusion imaging agent. Comparison with labeled phentermine derivatives.

A radioiodinated derivative of the anorexinergic drug phentermine was synthesized and evaluated as a potential brain imaging agent. Stoichiometric iodination of the intermediate 4-aminophentermine (AmP) gave a mixture of mono and diiodo products, while the radioiodination at the no-carrier-added (NCA) level gave 73% isolated yield of the 3-[125I]iodo-4-aminophentermine with less than 2% of the diiodo derivative. The tissue distribution of the radiochemical in rats showed that it was readily extracted by the brain followed by relatively slow clearance from that organ. However, a comparison with other labeled phentermine derivatives indicated that the total brain uptake, retention and selectivity of the new agent were poorer, probably as a result of the presence of the 4-amino substituent.