Preparation, biodistribution and dosimetry of copper-64-labeled anti-colorectal carcinoma monoclonal antibody fragments 1A3-F(ab{prime}){sub 2}
- Washington Univ. School of Medicine, St.Louis, MO (United States)
Antibody fragments labeled with a radiometal using bifunctional chelates generally undergo renal clearance followed by trapping of the metabolites, leading to high radiation doses to the kidneys. Copper-64-labeled BAT-2IT-1A3-F(ab{prime}){sub 2} was recently reported to accumulate in colorectal tumors in an animal model, however, kidney uptake was also high. In this study, the preparation of {sup 64}Cu-BAT-2IT-1A3-F(ab{prime}){sub 2} was optimized to reduce the renal uptake. The bifunctional chelate 6-bromoacetamidobenzyl-1,4,8,11-tetraazacyclotetradecane-N,N{prime},N{double_prime},N{prime}{double_prime}-tetraacetic acid (BAT) was conjugated to 1A3-F(ab{prime}){sub 2} using the linking agent 2-iminothiolane (2IT). The conjugation reaction produced 20% of a lower molecular weight impurity found to be TETA-1A3-Fab{prime}. The conjugation procedure was optimized to include FPLC purification of the BAT-2IT-1A3-F(ab{prime}){sub 2} from TETA-1A3-Fab{prime} after conjugation prior to labeling with {sup 64}Cu. The biodistribution of {sup 64}Cu-labeled FPLC-purified and unpurified conjugates was determined in normal Sprague-Dawley rats and tumor-bearing Golden Syrian hamsters. Human absorbed doses were calculated from rat biodistribution data and PET imaging of a baboon. Upon FPLC purification of the BAT-2IT-1A3-F(ab{prime}){sub 2}, the immunoreactivity of {sup 64}Cu-labeled 1A3-F(ab{prime}){sub 2} was significantly improved over that of non-FPLC-purified {sup 64}Cu-BAT-2IT-1A3-F(ab{prime}){sub 2}, and the kidney uptake was decreased in normal rats. The biodistribution in hamsters showed some improvement in both tumor uptake and kidney clearance with FPLC-purified {sup 64}Cu-BAT-2IT-1A3-F(ab{prime}){sub 2}.The improved dosimetry of {sub 64}Cu-labeled FPLC purified BAT-2IT-1A3-F(ab{prime}){sub 2} should more readily allow this agent to be investigated clinically to image colorectal cancer using PET. 33 refs., 7 figs., 3 tabs.
- OSTI ID:
- 252941
- Journal Information:
- Journal of Nuclear Medicine, Vol. 36, Issue 5; Other Information: PBD: May 1995
- Country of Publication:
- United States
- Language:
- English
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