Similarities and differences in 111In- and 90Y-labeled 1B4M-DTPA antiTac monoclonal antibody distribution.

Monoclonal antibodies (MoAb) labeled with 90 Y are being used for radioimmunotherapy. Because 90 Y is a beta emitter, quantitative information from imaging is suboptimal. With the concept of a matched pair of isotopes, 111 In is used as a surrogate marker for 90 Y. We evaluated the differences in biodistribution between 111 In- and 90 Y-labeled murine antiTac MoAb directed against the IL-2Rα receptor. Methods: The antiTac was conjugated to the 2-(4-isothiocyanatobenzyl)-6-methyl-diethylenethamine pentaacetic acid (1B4M-DTPA, also known as MX-DTPA). Nine patients with adult T-cell leukemia were treated. Patients received approximately 185 MBq (5 mCi) 111 In-labeled antiTac for imaging and 185-555 MBq (5-15 mCi) 90 Y-labeled antiTac for therapy. The immunoreactivity of 111 In-labeled antiTac was 90% ± 6%, whereas for 90 Y-labeled antiTac, it was 74% ± 12%. Results: The differences in blood and plasma kinetics of the two isotopes were small. The area undemeath the blood radioactivity curve was 1.91 percentage ± 0.58 percentage injected dose (%ID) × h/mL for 111 In and 1.86% ± 0.64 %ID × h/mL for 90 Y. Urinary excretion of 90 Y was significantly greater than that of 111 In in the first 24 h (P = 0.001), but later, the excretion of 111 In was significantly greater (P = 0.001 to P = 0.04). Core biopsies of bone marrow showed a mean of 0.0029 ± 0.0012 %ID/g for 111 In, whereas the 90 Y concentration was 0.0049 ± 0.0021 %ID/g. Analyses of activity bound to circulating cells showed concentrations of 500-30,000 molecules of antiTac per cell. When cell-bound activity was corrected for immunoreactive fraction, the ratio of 111 In to 90 Y in circulating cells was 1.11 ± 0.17. Three biopsies of tumor-involved skin showed ratios of 111 In to 90 Y of 0.7, 0.9 and 1.1. Conclusion: This study shows that differences typically ranging from 10% to 15% exist in the biodistribution between 111 In- and 90 Y-labeled antiTac. Thus, it appears that 111 In can be used as a surrogate marker for 90 Y when labeling antiTac with the 1B4M chelate, although underestimates of the bone marrow radiation dose should be anticipated.