Background: CC49, an antibody (mAb) reactive to tumor-associated glycoprotein (TAG-72), has been extensively studied for radioimmunotherapy for colon cancer. Myelotoxicity has been dose-limiting because of prolonged circulation time in the plasma, and human anti-mouse antibody responses were observed in the majority of patients. A CH2 domain deleted and humanized CC49 (HuCC49ΔCh2) was developed to ameliorate these problems. This study reports biodistribution and dosimetry of 111In/90Y- HuCC49ΔCh2 (IDEC-159). Materials and Methods: Five (5) patients with colon cancer were enrolled. Each patient received intravenous administration of 185 MBq 111In-HuCC49ΔCh2, followed by sequential gamma camera imaging, and blood counting. Uptakes and clearance half-lives for organs and tumors were quantified from images. Absorbed doses for 90Y- HuCC49ΔCh2 were derived from 111In-HuCC49ΔCh2 kinetic data. Results: Compared to reported 111In/90Y-CC49 data in the literature, median blood circulation T1/2β was less at 38 (31-43) hours for 90Y-HuCC49ΔCh2, than 50 hours for 90Y-CC49. Median tumor-to-marrow absorbed dose ratio was 18 for 90Y-HuCC49ΔCh2, and 9.53 for 90Y-CC49. Median tumor-to-liver absorbed dose ratio was 3.14 for 90Y-HuCC49ΔCh2, and 1.0 for 90Y-CC49. Median tumor-to-spleen absorbed dose was 3.19 for 90Y-HuCC49ΔCh2, and 1.07 for 90Y-CC49. Conclusions: A humanized and CH2 domain-deleted CC49 antibody radiolabeled with 111In/90Y showed improved tumor-to-normal dose ratios over those reported from studies with intact CC49. © Copyright 2011, Mary Ann Liebert, Inc.