Rhenium-186 labeling of CC49 monoclonal antibody with N-[TRIS[2-[[N-(benzyloxy) amino] carbonyl]-ethyl]methyl] succinamic acid, trisuccin and biodistribution studies
- Univ. of Alabama, Birmingham, AL (United States)
The use of hydroxamic acid derivatives as bifunctional chelating agents (BCAs) for radiolabeling of monoclonal antibodies, and the design and synthesis of the first member of this family, trisuccin, was recently reported. In this report, the Re-186 labeling of trisuccin-CC49 conjugate`s and their biodistribution in nude mice bearing human tumor xenografts are described. Synthesis of the BCA and conjugate preparation were as described before. Reduced (SnCl{sub 2}) Re-186 was used for labeling with 2-hydroxyisobutyric acid as the transfer ligand. The Re-186-labeled CC49 was then injected i.p. into nude mice bearing LS174T colon cancer xenografts. The injected animals were Imaged after 4 days and showed localization of the conjugate In the tumors. The biodistribution of Re-186-trisuccin-CC49 was determined at 2, 4, and 6 days after i.p. injection of 3 {mu}Ci of radioimmunoconjugate. The highest concentrations of the radioimmunoconjugate were found in tumor at all time points (6.4{plus_minus}0.9% ID/g at day 2 which decreased to 5.0{plus_minus}0.6% ID/g at 6 days after injection). The organs with the highest concentration were kidney (3.8{plus_minus}0.5% ID/g at day 2 and 1.2{plus_minus}0.1% ID/g at day 6) and liver (2.4% ID/g at day 2 and 1.3% ID/g at day 6). The tumor to normal tissue ratios for blood, kidney, and liver were 7.2, 1.7, and 2.1 at 6 days after injection, respectively. These results demonstrate that this now radioimmunoconjugate preferentially localized in the tumor.
- DOE Contract Number:
- FG05-93ER61654
- OSTI ID:
- 198107
- Report Number(s):
- CONF-940605--; CNN: Grant CA45232
- Journal Information:
- Journal of Nuclear Medicine, Journal Name: Journal of Nuclear Medicine Journal Issue: Suppl.5 Vol. 35; ISSN 0161-5505; ISSN JNMEAQ
- Country of Publication:
- United States
- Language:
- English
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