The ratio of maximum percent tumor accumulations of the pretargeting agent and the radiolabeled effector is independent of tumor size

Our previous studies have indicated that the optimal dosage ratio of pretargeting antibody to effector is proportional to their maximum percent tumor accumulations (MPTAs). This study quantitatively describes how both MPTAs and their ratio change with tumor size, to simplify pretargeting optimization when tumor size varies. The CC49 antibody dosages below saturation of the tumor antigen level were first examined for the LS174T tumor mouse model. Then the MPTAs of the antibody in mice bearing tumors of different size were determined, always at antibody dosages below antigen saturation. Historical data from this laboratory were used to collect the MPTAs of the 99mTc-cMORF effector for different tumor sizes, always at effector dosages below that required to saturate the MORF in tumor. The MPTAs vs tumor sizes for both the antibody and the effector were fitted non-linearly. The best fit of the antibody MPTA (Yantibody) with tumor size (x) in grams was Yantibody = 19.00 x\^-0.65 while that for the effector was Yeffector = 4.51 x\^-0.66. Thus, even though the MPTAs of both vary with tumor size, the ratio (Yantibody/ Yeffector) is a constant at 4.21. In conclusion, the MPTA ratio of the antibody to the effector was found to be constant with tumor size, an observation that will simplify pretargeting optimization because remeasurement of the optimum dosage ratio for different tumor sizes can be avoided. Theoretical considerations also suggest that this relationship may be universal for alternative antibody/effector pairs and for different target models, but this must be experimentally confirmed.