The ratio of maximum percent tumor accumulations of pretargeting agent and radiolabeled effector does not change with tumor size

Objectives The optimal dosage ratio of antibody to effector in pretargeting is proportional to the ratio of their maximum percent tumor accumulations (MPTAs). As a complication to dosage optimization, each MPTA varies with tumor size differently. However, if it can be shown that the ratio of MPTAs is a constant with tumor size, the optimal dosage ratio determined for one tumor size will be applicable to all others, thereby greatly simplifying dosage optimization.

Methods After the dosage range providing the MPTAs of the ¹¹¹In labeled pretargeting antibody antiTAG72 CC49 was located, the MPTAs were measured in the LS174T tumored mice bearing different size tumors. The influence of tumor size on the MPTAs of the effector, ^99mTc-cMORF, was determined by collecting the results of previous studies. In both cases, the MPTAs vs tumor sizes were fitted non-linearly with the same power function.

Results The best fit of the antibody MPTA (y) with tumor size (x) was y=18.99 x ^-0.65 while that for the effector was y=4.51 x ^-0.66. Thus even though the MPTAs of both change dramatically with tumor size, the ratio remains constant.

Conclusions The MPTA ratio of antibody to effector is a constant of tumor size. Optimization will be greatly simplified since the optimum dosage ratio does not require remeasurement for different tumor sizes. Theoretical considerations suggest that this relationship will also hold for alternative antibodies and effectors but this must be confirmed.