Effect of metabolism on retention of indium-111-labeled monoclonal antibody in liver and blood
- National Cancer Institute, Bethesda, MD (United States); and others
The effect of a chelator structure on the metabolic fate of the {sup 111}In-labeled monoclonal antibody (Mab) T101 was investigated in normal Balb/c mice to assess the importance of this chemical parameter in the reduction of the background radioactivity in blood and liver. Mab T101 was conjugated with either 2-(p-isothiocyanatobenzyl)-6-methyl-diethylaminetriaminepentaacetic acid (DTPA) (1B4M), 2-(p-isothiocyanatobenzyl) cyclohexyl-DTPA (CHX-B) or cyclic DTPA dianhydride (cDTPA) and then radiolabeled with {sup 111}In-labeled T101 conjugates and sacrificed in groups of five up to 5 days postinjection for comparative biodistribution studies and analyses of liver, blood and urine samples for radioindium products. The biodistribution of {sup 111}In-1B4M-T101 and {sup 111}In-CHX-B-T101 were similar to each other but significantly different from that of {sup 111}In-cDTPA-T101, particularly in the blood and liver. Size-exclusion high-performance liquid chromatography indicated that the concentration of the intact {sup 111}In-immunoglobulin (Ig)G in liver decreased with similar rates for the three conjugates. Meanwhile, the concentration of a small DTPA-like metabolite in liver increased to a different peak value (4.6% 1D/g for the cDTPA conjugate and 1.6% lD/g for the 1B4M and CHX-B conjugates) approximately at 24 hr and maintained a steady-state concentration up to 5 days. The thiourea linkage between T101 and the {sup 111}In-labeled chelates and a higher complex stability and higher lipophilicity of {sup 111}In-1B4M and {sup 111}In-CHX-B appear to be responsible for lower liver and higher blood radioactivity for the 1B4M and CHX conjugates. 31 refs., 3 figs., 1 tab.
- OSTI ID:
- 114870
- Journal Information:
- Journal of Nuclear Medicine, Vol. 35, Issue 11; Other Information: PBD: Nov 1994
- Country of Publication:
- United States
- Language:
- English
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