Pharmacokinetics, biodistribution and dosimetry of Tc-99m-labeled anti-human epidermal growth factor receptor humanized monoclonal antibody R3 in rats

The pharmacokinetics, biodistribution and dosimetry of Tc-99m-labeled anti-human epidermal growth factor receptor (anti-hEGF-r) humanized monoclonal antibody (MAb) R3 was investigated following intravenous injection in normal Wistar rats, Serum disappearance curves were best fit by a two-compartment model having a mean distribution half-life (t(1/2 alpha)) of 0.250 h and a mean elimination (t(1/2 beta)) of 13.89 h. Among the various organs, a little accumulation of the radiolabeled antibody was found only in kidneys. Biodistribution and dosimetry studies in humans were performed by extrapolation of the animal data to humans. Absorbed dose to normal organs and the remainder of the whole body were estimated using the medical internal radiation dose formula, and dose contributions from radioactivity in transit through the gastrointestinal tract were estimated using a compartment model, Extrapolated values of radiation absorbed dose to normal organs in rads per millicurie administered were whole body, 0.0085; lower large intestine wall, 0.0898; small intestine, 0.0530; upper large intestine wall, 0.0731; and kidneys, 0.0455. The effective dose equivalent predicted was 0.0162 rem/mCi and the effective dose was found to be 0.015 rem/mCi. On the basis of the pharmacokinetics, biodistribution and internal radiation dosimetry information obtained in this study, a diagnostic phase I clinical trial with Tc-99m-labeled humanized MAb R3 conjugate in patients should be supported. (C) 1998 Elsevier Science Inc.