CALCULATED AND TLD-BASED ABSORBED DOSE ESTIMATES FOR I-131-LABELED 3F8 MONOCLONAL-ANTIBODY IN A HUMAN NEUROBLASTOMA XENOGRAFT NUDE-MOUSE MODEL

Preclinical evaluation of the therapeutic potential of radiolabeled an tibodies is commonly performed in a xenografted nude mouse model. To a ssess therapeutic efficacy it is important to estimate the absorbed do se to the tumor and normal tissues of the nude mouse. The current stud y was designed to accurately measure radiation does to human neuroblas toma xenografts and normal organs in nude mice treated with I-131-labe led 3F8 monoclonal antibody (MoAb) against disialoganglioside GD(2) an tigen. Absorbed dose estimates were obtained using two different appro aches: (1) measurement with teflon-imbedded CaSO4:Dy mini-thermolumine scent dosimeters (TLDs) and (2) calculation using mouse S-factors. The calculated total dose to tumor one week after i.v. injection of the 5 0 mu Ci I-131-3F8 MoAb was 604 cGy. The corresponding decay corrected and not corrected TLD measurements were 109 +/- 9 and 48.7 +/- 3.4 cGy respectively. The calculated to TLD-derived dose ratios for tumor ran ged from 6.1 at 24 h to 5.5 at I week. The light output fading rate wa s found to depend upon the tissue type within which the TLDs were impl anted. The decay rate in tumor, muscle, subcutaneous tissue and in vit ro, were 9.5, 5.0, 3.7 and 0.67% per day, respectively. We have demons trated that the type of tissue in which the TLD was implanted strongly influenced the in vine decay of light output. Even with decay correct ion, a significant discrepancy was observed between MIRD-based calcula ted and CaSO4:Dy mini-TLD measured absorbed doses. Batch dependence, p H of the tumor or other variables associated with TLDs which are not a s yet well known may account for this discrepancy.