Journal of Clinical Oncology, Vol 8, 1894-1906, Copyright © 1990 by American Society of Clinical Oncology
Quantitative analysis of antibody localization in human metastatic colon cancer: a phase I study of monoclonal antibody A33
S Welt, CR Divgi, FX Real, SD Yeh, P Garin-Chesa, CL Finstad, J Sakamoto, A Cohen, ER Sigurdson and N Kemeny
Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
A33 is a mouse immunoglobulin G2a (IgG2a) monoclonal antibody (mAb) that
detects a heat-stable, protease- and neuraminidase-resistant epitope. The
antigen is homogeneously expressed by virtually all colon cancers and in
the colon mucosa but not other epithelial tissues. The biodistribution and
imaging characteristics of iodine-131 (131I)-mAbA33 were studied in
colorectal carcinoma patients with hepatic metastases. Antibody labeled
with 2 to 5 mCi of 131I was administered intravenously (IV) 7 to 8 days
before surgery at five dose levels, ranging from 0.2 mg to 50 mg, with
three or more patients entered at each dose level. In addition, three
patients received 2 mg 131I-mAbTA99 (an isotype-matched control mAb)
together with 125I-mAbA33. Evaluation included whole-body imaging with a
gamma camera, technetium-99 (99mTc)-human serum albumin blood pool scans,
liver/spleen scans, abdominal computed tomographic (CT) scans, hepatic
arteriograms, antibody pharmacokinetics, and assessment of antibody
distribution in biopsied malignant and normal tissues. Selective mAbA33
localization to tumor tissue was demonstrated in 19 of 20 patients, and
external imaging correlated with surgical inspection, pathologic
examination, and tissue radioactivity. One week after antibody
administration, tumor:liver ratios ranged from 6.9:1 to 100:1 and
tumor:serum ratios from 4.1:1 to 25.2:1. 99mTc-albumin blood pool studies
showed that liver metastases were hypovascular, emphasizing the selective
localization of mAbA33 despite poor tumor- blood flow. Control mAbTA99
studies showed mAbA33 localization was antigen-specific; tumor:liver ratios
were 2.3- to 45-fold higher for specific antibody. In metastatic lesions,
radioisotope was localized primarily in the viable periphery; however, even
the necrotic tumor core concentrated specific antibody. External imaging
showed isotope visualization in some patients' large bowel; whether this
represents specific antibody uptake or gastric iodine secretion is unclear.
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