TY - JOUR T1 - <sup>124</sup>I-huA33 Antibody PET of Colorectal Cancer JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1173 LP - 1180 DO - 10.2967/jnumed.110.086165 VL - 52 IS - 8 AU - Jorge A. Carrasquillo AU - Neeta Pandit-Taskar AU - Joseph A. O'Donoghue AU - John L. Humm AU - Pat Zanzonico AU - Peter M. Smith-Jones AU - Chaitanya R. Divgi AU - Daniel A. Pryma AU - Shutian Ruan AU - Nancy E. Kemeny AU - Yuman Fong AU - Douglas Wong AU - Jaspreet S. Jaggi AU - David A. Scheinberg AU - Mithat Gonen AU - Katherine S. Panageas AU - Gerd Ritter AU - Achim A. Jungbluth AU - Lloyd J. Old AU - Steven M. Larson Y1 - 2011/08/01 UR - http://jnm.snmjournals.org/content/52/8/1173.abstract N2 - Humanized A33 (huA33) is a promising monoclonal antibody that recognizes A33 antigen, which is present in more than 95% of colorectal cancers and in normal bowel. In this study, we took advantage of quantitative PET to evaluate 124I huA33 targeting, biodistribution, and safety in patients with colorectal cancer. We also determined the biodistribution of 124I-huA33 when a large dose of human intravenous IgG (IVIG) was administered to manipulate the Fc receptor or when 124I-huA33 was given via hepatic arterial infusion (HAI). Methods: We studied 25 patients with primary or metastatic colorectal cancer; 19 patients had surgical exploration or resection. Patients received a median of 343 MBq (44.4–396 MBq) and 10 mg of 124I-huA33. Nineteen patients received the antibody intravenously and 6 patients via HAI, and 5 patients also received IVIG. Results: Ten of 12 primary tumors were visualized in 11 patients. The median concentration in primary colon tumors was 0.016% injected dose per gram, compared with 0.004% in normal colon. The PET-based median ratio of hepatic tumor uptake to normal-liver uptake was 3.9 (range, 1.8–22.2). Quantitation using PET, compared with well counting of serum and tissue, showed little difference. Prominent uptake in bowel hindered tumor identification in some patients. Pharmacokinetics showed that patients receiving IVIG had a significantly shorter serum half-time (41.6 ± 14.0 h) than those without (65.2 ± 9.8 h). There were no differences in clearance rates among the intravenous group, IVIG group, and HAI group, nor was there any difference in serum area under the curve, maximum serum concentration, or volume of distribution. Weak titers of human–antihuman antibodies were observed in 6 of 25 patients. No acute side effects or significant toxicities were associated with huA33. Conclusion: Good localization of 124I-huA33 in colorectal cancer with no significant toxicity has been observed. PET-derived 124I concentrations agreed well with those obtained by well counting of surgically resected tissue and blood, confirming the quantitative accuracy of 124I-huA33 PET. The HAI route had no advantage over the intravenous route. No clinically significant changes in blood clearance were induced by IVIG. ER -