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) up take 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 wer e treated with 4.4 MBq (120 mu Ci) of Y-90-labeled anti-Carcinoembryon ic Antigen Mab (Y-90-ZCE025). Regression analysis demonstrated an inve rse log-log relationship of antibody uptake (%ID/g) to tumor mass in f our 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. Xen ograft radiation dose was obtained by temporal integration of each cur ve and application of appropriate dose estimation formulas. For each a ssumed tumor mass, an edge correction for loss of beta energy outside the target volume was applied assuming a spherical tumor shape. Estima ted average absorbed doses were found to vary only from 13.8-10.3 Gy f or a 20-fo1d change in tumor sizes (0.1-2.0 g, respectively). Such con stancy of dose may explain xenograft stasis observed by our group in e arlier experiments at this level of administered Y-90 activity.