COMPARISON OF THE TARGETING CHARACTERISTICS OF VARIOUS RADIOIMMUNOCONJUGATES FOR RADIOIMMUNOTHERAPY OF NEUROBLASTOMA - DOSIMETRY CALCULATIONS INCORPORATING CROSS-ORGAN BETA DOSES

To optimize the efficacy of radioimmunotherapy (RIT), the ideal antibo dy-radioisotope combinations should be used to deliver the highest tum or and the lowest normal tissue doses. In a mouse model, tumor and cri tical organ-absorbed doses delivered by different radioimmunoconjugate s were calculated and compared. We used a Medical Internal Radiation D osimetry (MIRD)-style mouse dosimetry model that incorporates cross-or gan beta doses to make refined estimates of the radiation absorbed dos e to tissues. Biodistribution data from neuroblastoma xenografted nude mice were used to estimate tumor, organ and bone marrow absorbed dose values for Y-90-3F8, I-131-3F8 and I-131-F(ab')(2) fragments. Immunor eactive fractions of the radiolabeled antibodies were comparable. Alth ough tumor uptake of the radioiodinated and radiometal labeled 3F8 was much higher than that of the radioiodinated F(ab')(2) fragments (maxi mum percent injected dose per gram values were 39.4, 33.2 and 20.1 for I-131-3F8, Y-90-3F8 and I-131-F(ab')(2), respectively), tumor to nont umor ratios were higher for radioiodinated fragments (with the excepti on of tumor to kidney ratio). For the minimum tumor dose necessary for complete ablation, the bone marrow received 195, 278 and 401 cGy for I-131-F(ab')2, I-131-3F8 and Y-90/3F8, respectively. Tumor doses were 50.1, 232 and 992 cGy/MBq for I-131-F(ab')(2), I-131-3F8 and Y-90-3F8, respectively. Tumor to bone marrow dose, which is defined as the ther apeutic index, was 21.5, 14.7 and 10.4 for I-131-F(ab')(2), I-131-3F8 and Y-90-3F8. I-131-F(ab')(2) fragments produced the highest therapeut ic index but also the lowest tumor dose for radioimmunotherapy. Radiom etal conjugated IgG produced the highest tumor dose but also the lowes t therapeutic index.