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Similarities and differences in 111In- and 90Y-labeled 1B4M-DTPA antiTac monoclonal antibody distribution. 1999

J A Carrasquillo, and J D White, and C H Paik, and A Raubitschek, and N Le, and M Rotman, and M W Brechbiel, and O A Gansow, and L E Top, and P Perentesis, and J C Reynolds, and D L Nelson, and T A Waldmann
Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Monoclonal antibodies (MoAb) labeled with 90Y are being used for radioimmunotherapy. Because 90Y is a beta emitter, quantitative information from imaging is suboptimal. With the concept of a "matched pair" of isotopes, 111In is used as a surrogate markerfor90Y. We evaluated the differences in biodistribution between 111In- and 90Y-labeled murine antiTac MoAb directed against the IL-2Ralpha receptor. METHODS The antiTac was conjugated to the 2-(4-isothiocyanatobenzyl)-6-methyl-diethylenetriamine 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) 111In-labeled antiTac for imaging and 185-555 MBq (5-15 mCi) 90Y-labeled antiTac for therapy. The immunoreactivity of 111In-labeled antiTac was 90%+/-6%, whereas for 90Y-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) x h/mL for 111In and 1.86%+/-0.64 %ID x h/mL for 90Y. Urinary excretion of 90Y was significantly greater than that of 111In in the first 24 h (P = 0.001), but later, the excretion of 111In 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 111In, whereas the 90Y 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 111In to 90Y in circulating cells was 1.11+/-0.17. Three biopsies of tumor-involved skin showed ratios of 111In to 90Y of 0.7, 0.9 and 1.1. CONCLUSIONS This study shows that differences typically ranging from 10% to 15% exist in the biodistribution between 111In- and 90Y-labeled antiTac. Thus, it appears that 111In can be used as a surrogate marker for 90Y when labeling antiTac with the 1 B4M chelate, although underestimates of the bone marrow radiation dose should be anticipated.

UI MeSH Term Description Entries
D007205 Indium Radioisotopes Unstable isotopes of indium that decay or disintegrate emitting radiation. In atoms with atomic weights 106-112, 113m, 114, and 116-124 are radioactive indium isotopes. Radioisotopes, Indium
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D002614 Chelating Agents Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS. Chelating Agent,Chelator,Complexons,Metal Antagonists,Chelators,Metal Chelating Agents,Agent, Chelating,Agents, Chelating,Agents, Metal Chelating,Antagonists, Metal,Chelating Agents, Metal
D004369 Pentetic Acid An iron chelating agent with properties like EDETIC ACID. DTPA has also been used as a chelator for other metals, such as plutonium. DTPA,Diethylenetriamine Pentaacetic Acid,Pentetates,Penthanil,Ca-DTPA,CaDTPA,CaNa-DTPA,Calcium Trisodium Pentetate,DETAPAC,Indium-DTPA,Mn-Dtpa,Pentacin,Pentacine,Pentaind,Pentetate Calcium Trisodium,Pentetate Zinc Trisodium,Sn-DTPA,Zinc-DTPA,Indium DTPA,Pentaacetic Acid, Diethylenetriamine,Pentetate, Calcium Trisodium,Zinc DTPA
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D015021 Yttrium Radioisotopes Unstable isotopes of yttrium that decay or disintegrate emitting radiation. Y atoms with atomic weights 82-88 and 90-96 are radioactive yttrium isotopes. Radioisotopes, Yttrium

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