Yttrium-90 DOTA peptide chimeric L6 toxicity and therapeutic potential in nude mice with human breast tumors
- Univ. of California at Davis, Sacramento, CA (United States); and others
Chimeric L6 MoAb (ChL6) as I-131 ChL6 has shown therapeutic promise for radioimmunotherapy in breast cancer patients. In order to enhance this therapeutic potential, we have developed an yttrium-90 (Y-90) ChL6 radiopharmaceutical by conjugating Y-90 DOTA peptide to ChL6 using DOTA-Gly-3L(p-isothiocyanato)-Phe-NH2. This DOTA peptide forms neutral complexes with trivalent metals allowing excess chelating agents and divalent metal complexes to be removed by ion exchange chromatography prior to conjugation, thus yielding a high Y-90/DOTA ratio on the final immune conjugate. Groups of 9-10 nude mice bearing subcutaneous 40-200 mg HBT 3477 xenographs were given 150,250,350,400,450 or 500 {mu}Ci of Y-90 DOTA peptide ChL6 (specific activity 1.1-3.5 {mu}Ci/{mu}g). Live cell immunoreactivity was 73-80% and 100% Y-90 moved with ChL6 on SEC3000 HPLC and TLC. Peripheral blood counts, weight, tumor size, blood and body clearance of Y-90 were monitored for 10 weeks. Whole body autoradiography was performed at 1,3 and 5 days post injection at the 250 and 450 {mu}Ci dose levels. No mouse that received less than 450 {mu}Ci of Y-90 died. The LD50/30 was 479 {mu}Ci. The nadirs of RBC, WBC and platelets were 10-20 days post 479 {mu}Ci. The nadirs of RBC, WBC and platelets were 10-20 days post injection. The depth of the nadir was dose dependent but occured in all groups. In the lowest dose group having substantial tumor response (350{mu}Ci) mean tumor volume decreased by >50% and 5 of 19 tumors completely regressed over the 10 week follow-up. This is the greatest LD50/30 for Y-90 immunoconjugate reported in nude mice to date. These results confirm the significance of the biodistribution and autoradiographic studies demonstrating tumor uptake of 18 {plus_minus} 8% ID/gm with 3/1 tumor to liver and 8/1 tumor to bone ratios 1, 3, and 5 days post injection.
- OSTI ID:
- 197987
- Report Number(s):
- CONF-940605--
- Journal Information:
- Journal of Nuclear Medicine, Journal Name: Journal of Nuclear Medicine Journal Issue: Suppl.5 Vol. 35; ISSN JNMEAQ; ISSN 0161-5505
- Country of Publication:
- United States
- Language:
- English
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