Biodistribution and radiation dosimetry of the α7 nicotinic acetylcholine receptor ligand [11C]CHIBA-1001 in humans

Introduction: 4-[C-11]Methylphenyl 2,4-diazabicyclo[3.2.2]nonane-2-carboxylate ([C-11]CHIBA-1001) is a newly developed positron emission tomography (PET) ligand for mapping alpha(7) nicotinic acetylcholine receptors. We investigated whole-body biodistribution and radiation dosimetry of [C-11]CHIBA-1001 in humans and compared the results with those obtained in mice. Methods: Dynamic whole-body PET was carried out for three human subjects after administering a bolus injection of [C-11]CHIBA-1001. Emission scans were collected in two-dimensional mode over five bed positions. Regions of interest were placed over 12 organs. Radiation dosimetry was estimated from the residence times of these source organs using the OLINDA program. Biodistribution data from mice were also used for the prediction of radiation dosimetry in humans, and results with and those without accommodation of different proportions of organ-to-total-body mass were compared with the results from the human PET study. Results: lit humans, the highest accumulation was observed in the liver, whereas in mice, the highest accumulation was observed in the urinary bladder. The estimated effective dose from the human PET study was 6.9 mu Sv/MBq, and that from mice was much underestimated. Conclusion: Effective dose estimates for [C-11]CHIBA-1001 were compatible with those associated with other common nuclear medicine tests. Absorption doses among several organs were considerably different between the human and mouse studies. Human dositmetry studies for the investigation of radiation safety are desirable as one of the first clinical trials of new PET probes before their application in subsequent clinical investigations. (C) 2011 Elsevier Inc. All rights reserved.