In vivo biodistribution of (IPIP)-I-125 and internal dosimetry of (IPIP)-I-123 radioiodinated agents selective to the muscarinic acetylcholinergic receptor complex

The development of new radioiodinated ligands for imaging the muscarinic ac etylcholinergic complex (mAChR) using single photon emission computed tomog raphy (SPECT) requires the evaluation of human organ doses prior to approva l for human use. Animal biodistribution and excretion data were obtained an d evaluated for IPIP, a new mAChR agent. Preliminary biodistribution studie s were performed on four different stereoisomers of IPIP. A biokinetic mode l of the Z-(S)-IPIP stereoisomer was constructed for the rat and used to es timate the internal absorbed dose in humans based on an extrapolation of th e rat model. The thyroid is the critical organ for this radiopharmaceutical , with an absorbed dose estimate of 2.4 mGy/MBq for both males and females, when labeled with I-123. Even when blocked, the thyroid is still the criti cal organ, yet with a 90% dose reduction. The heart and brain receive the n ext highest doses in both males and females. Effective dose estimates for t he use of pure I-123-PIP in humans are 0.16 mSv/MBq for males and 0.14 mSv/ MBq for females: The biodistribution studies of the Z-(S)-IPIP stereoisomer showed the most promise as a successful agent for imaging muscarinic recep tor sites in the heart and brain. IPIP also demonstrated potential as a the rapeutic radiopharmaceutical for some colon carcinomas where muscarinic rec eptor sites are expressed in the tumor cells. These results provide prelimi nary data for use of IPIP in clinical studies on humans. (C) 2000 American Association of Physicists in Medicine.