Synapse - (124)I-huA33 antibody PET of colorectal cancer

(124)I-huA33 antibody PET of colorectal cancer Journal Article

Authors:	Carrasquillo, J. A.; Pandit-Taskar, N.; O'Donoghue, J. A.; Humm, J. L.; Zanzonico, P.; Smith-Jones, P. M.; Divgi, C. R.; Pryma, D. A.; Ruan, S.; Kemeny, N. E.; Fong, Y.; Wong, D.; Jaggi, J. S.; Scheinberg, D. A.; Gonen, M.; Panageas, K. S.; Ritter, G.; Jungbluth, A. A.; Old, L. J.; Larson, S. M.
Article Title:	(124)I-huA33 antibody PET of colorectal cancer
Abstract:	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. Copyright © 2011 by the Society of Nuclear Medicine, Inc.
Keywords:	adult; cancer survival; clinical article; controlled study; aged; unclassified drug; area under the curve; drug safety; prospective study; colorectal cancer; controlled clinical trial; immunoglobulin; drug distribution; drug uptake; quantitative analysis; radiopharmaceutical agent; drug clearance; colorectal surgery; cell count; open study; metastasis potential; drug blood level; drug half life; absence of side effects; colon; antibody; antibody titer; positron; 124i; arterial; a33; monoclonal antibody a 33 i 124
Journal Title:	Journal of Nuclear Medicine
Volume:	52
Issue:	8
ISSN:	0161-5505
Publisher:	Society of Nuclear Medicine
Date Published:	2011-08-01
Start Page:	1173
End Page:	1180
Language:	English
DOI:	10.2967/jnumed.110.086165
PROVIDER:	scopus
PMCID:	PMC3394182
PUBMED:	21764796
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-80051675838&partnerID=40&md5=a1ce732feb5d038324ee5e29443ef62c
Notes:	--- - "Cited By (since 1996): 1" - "Export Date: 3 October 2011" - "CODEN: JNMEA" - "Source: Scopus"