Adding an avidin clearing agent improved MORF pretargeting of tumor

Abstract

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Objectives: This laboratory is successfully using MORF/cMORF pretargeting to accumulate radioactivity in tumor xenografts in mice but without benefit of a clearing agent. We have now investigated the improvement in pretargeting by injecting an avidin intermediate between the biotinylated MORF-antibody and the 99mTc labeled cMORF effector. As in all recent studies of pretargeting from this laboratory, a semiempirical prediction model was used to estimate the optimum dosages.

Methods: After conjugating CC49 with both biotin and MORF, measuring gpm and confirming specificity for tumor cells, the MORF-CC49-biotin was used in a 3-step protocol in normal mice in which increasing dosages of avidin was added intermediate between the biotinylated antibody and 99mTc-cMORF. The dosages of antibody and cMORF were estimated using our semiempirical model from the pharmacokinetics of each injectate evaluated separately. Thereafter, a pretargeting protocol was designed and applied to LS174T tumored mice.

Results: Under one set of variables (30 µg of MORF-CC49-biotin, 1 day pretargeting interval, 3 h clearing time, 1.2 µg of 99mTc-cMORF, and 3 h detection time), the clearance efficiency in normal mice was found to be about 60 % for avidin dosages greater than 20 µg. In tumored mice, the same set of variables was used to obtain the identical clearance efficiency. As predicted, tumor accumulation was unchanged at 6.30 %ID/g for tumors of 0.70 g, while the tumor/tissue ratios increased three fold for blood and less for other tissues.

Conclusions: Using a semiempirical prediction model to simplify dosage selection, MORF/cMORF pretargeting of tumor was improved by adding an avidin clearance step.