PMID: 9179227May 1, 1997Paper

Yttrium-90/indium-111-DOTA-peptide-chimeric L6: pharmacokinetics, dosimetry and initial results in patients with incurable breast cancer

Anticancer Research
S J DeNardoG L DeNardo

Abstract

Radioimmunotherapy (RIT) using 131I-Chimeric L6 (ChL6) antibody has shown therapeutic promise for patients with breast cancer. To enhance this potential, a novel immunoconjugate was developed that targets adenocarcinomas like breast cancer and tightly binds yttrium-90 (90Y) for therapy and indium-111 (111In) for imaging. The radioimmunoconjugate consists of a macrocyclic chelator (DOTA) linked to ChL6 by a catabolizable peptide. 90Y-DOTA-peptide-ChL6 was designed to minimize the radiation dose to critical normal tissues, thereby improving the therapeutic index. Three patients with incurable metastatic breast cancer received 90Y/111In-DOTA-peptide-ChL6 for 5 pharmacokinetics/dosimetry studies and one of these patients also received 2 therapy doses. Quantitative imaging of 111In and in vitro assay of 90Y and 111In in blood urine and bone marrow samples were obtained. 90Y/111In-DOTA-peptide-ChL6 was prepared at high purity and was stable in vivo. Assays of bone marrow revealed no evidence for escape of 90Y or 111In from the chelate. 111In imaging of tumors was excellent, providing a therapeutic index for tumor to marrow radiation as high as 229 to 1. 90Y and 111In provided comparable pharmacokinetics, as did tracer and therapeutic...Continue Reading

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