A method including edge effects for the estimation of radioimmunotherapy absorbed doses in the tumor xenograft model

The temporal relationship of radiolabeled monoclonal antibody (Mab) uptake to tumor size in a nude mouse human colon cancer xenograft model (LS174T) was evaluated as an aid to developing a method for estimation of radioimmunotherapy absorbed dose. Tumors of heterogeneous size were treated with 4.4 MBq (120 microCi) of 90Y-labeled anti-Carcinoembryonic Antigen Mab (90Y-ZCE025). Regression analysis demonstrated an inverse log-log relationship of antibody uptake (%ID/g) to tumor mass in four time intervals investigated (N > 10 points/interval):12-24 h, 2-3 d, 5-7 d, and 10-14 d. Curves of predicted radionuclide concentration vs time were then constructed for a range of constant tumor sizes. Xenograft radiation dose was obtained by temporal integration of each curve and application of appropriate dose estimation formulas. For each assumed tumor mass, an edge correction for loss of beta energy outside the target volume was applied assuming a spherical tumor shape. Estimated average absorbed doses were found to vary only from 13.8-10.3 Gy for a 20-fold change in tumor sizes (0.1-2.0 g, respectively). Such constancy of dose may explain xenograft stasis observed by our group in earlier experiments at this level of administered 90Y activity.