Two-step targeting and dosimetry for small cell lung cancer xenograft withanti-NCAM/antihistamine bispecific antibody and radioiodinated bivalent hapten

The "affinity enhancement system," a two-step targeting technique using bis pecific antibody and radiolabeled bivalent hapten, has been reported to be useful for carcinoembryonic antigen-expressing tumors. The purpose of this study was to evaluate the efficacy of this method for targeting human small cell lung cancer using an antineural cell adhesion molecule antibody. Meth ods: Antineural cell adhesion molecule/antihistamine bispecific antibody NK 1NBL1-679 was prepared by coupling an equimolecular quantity of a Fab' frag ment of NK1NBL1 to a Fab fragment of antihistamine 679. Athymic mice inocul ated with NCI-H69 small cell lung cancer cells expressing neural cell adhes ion molecule were administered bispecific antibody and then 48 h later I-12 5-labeled bivalent histamine hapten. I-125-labeled intact NK1NBL1 was injec ted into other groups of mice. Biodistributions were examined as a function of time. Results: In mice of the two-step targeting, tumor uptake was 2.5 +/- 0.2, 3.2 +/- 0.4, 6.4 +/- 2.0, 7.2 +/- 2.7, 6.1 +/- 2.1 and 2.2 +/- 0.4 %ID/g at 5, 30 min, 5, 24, 48 and 96 h, and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios were 1.4 +/- 1.1, 10.8 +/- 13.2 and 4.6 +/- 4.7 , respectively, at 5 h, whereas I-125-labeled NK1NBL1 showed a tumor uptake of 5.7 +/- 0.4 %ID/g and tumor-to-blood, tumor-to-liver and tumor-to-kidne y ratios of 0.3 +/- 0.1, 1.1 +/- 0.2 and 0.9 +/- 0.1, respectively, at 5 h. These results were confirmed by autoradiographic studies, which demonstrat ed clear tumor-to-normal tissue contrast. Dosimetry showed that the affinit y enhancement system could enhance the therapeutic potential of the antineu ral cell adhesion molecule antibody NK1NBL1. Conclusion: This two-step targ eting method seems promising for the diagnosis and therapy of small cell lu ng cancer.