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Radiolocalization of Xenografted Human Lung Cancer with Monoclonal Antibody 8 in Nude Mice¹

Department of Surgery, Institute of Clinical Medicine [K. E.], Pathology Division, Tsukuba University Hospital [H. K.], and Department of Pathology, Institute of Basic Medical Sciences [T. O.], University of Tsukuba, Sakura-mura, Niihari-gun, Ibaraki-ken 305, Japan

A monoclonal antibody (MAb) 8 [immunoglobulin G3 (IgG3)], directed against a M_r 48,000 human lung cancer-associated antigen, was radiolabeled with either ¹²⁵I or ¹³¹I, and its biodistribution was studied in nude mice bearing human lung cancer (TKB-2) over a 7-day period. ¹²⁵I-labeled MAb 8 increased its binding to the tumor during the period, while the binding of ¹²⁵I-labeled control IgG3 declined after initial uptake. At Day 7, percentages of injected dose of ¹²⁵I-labeled MAb 8 bound to the tumor rose to 7.4%, which was a 4.4-fold increase from Day 1 and 16-fold binding of ¹²⁵I-labeled control IgG3 at the same day. Tumor:blood ratios became 2.7:1 at Day 7, and tumor:liver, tumor:spleen, and tumor:kidney ratios were more than 9:1. Normal organs showed no significant uptake of ¹²⁵I-labeled MAb 8, compared with those of ¹²⁵I-labeled control IgG3. A clear image of the xenografted tumor was obtained at Day 5, and it further improved at Day 7, when 60% of whole body radioactivity was localized to the tumor. Autoradiography of the mouse with tumor confirmed the excellent localization of ¹²⁵I-labeled MAb 8 to the tumor, although the radioactivity of the tumor was not uniformly distributed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that most of the radioactivity was present at the tumor in the form of degraded immunoglobulin. MAb 8 has a potential usefulness in the diagnosis and treatment of lung cancer.

¹ This study was supported in part by a grant from the Japanese Ministry of Education, Science and Culture (No. 61771005).

² To whom requests for reprints should be addressed.

Received 11/ 5/86. Revised 6/29/87. Accepted 7/23/87.