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Pharmacokinetics, Immune Response, and Biodistribution of Iodine-131-Labeled Chimeric Mouse/Human IgG1,k 17-1A Monoclonal Antibody

Comprehensive Cancer Center, Departments of Radiation Oncology, Nuclear Medicine and Medicine, University of Alabama at Birmingham, Alabama
Veteran's Administration Medical Center, Birmingham, Alabama
Centocor, Inc., Seattle, Washington

Correspondence: For reprints contact: M.B. Khazaeli, PhD, Comprehensive Cancer Center, University of Alabama at Birmingham, Lurleen Wallace Tumor Institute—Room 262, UAB Station, Birmingham, Alabama 35294.

ABSTRACT

Pharmacokinetics, immunogenicity,and biodistribution of a ¹³¹I-labeled mouse/human chimeric monoclonal antibody (C-17-1A) was studied in six metastatic colon cancer patients. Pharmacokinetics obtained from serum radioactivity or chimera concentration were identical after 5 mCi of ¹³¹I-C-17-1A with mean alpha half-lives of 17.6 ± 2.3 and 19.7 ± 2.9 and mean beta half-lives of 100.9 ± 16.1 and 106.4 ± 14.1 hr, respectively. HPLC analysis documented the monomeric chimeric 17-1A without evidence of immune complexes or free ¹³¹I. None of the patients developed antibody after ¹³¹I-chimeric 17-1A exposure. Radiolocalization occurred in known areas of disease >4 cm in all patients. The half-life of total-body radioactivity was 58 ± 7 hr by whole-body counts and 64 ± 13 hr by urine measurements. Whole-body and bone marrow dose estimates ranged from 0.75–1.03 and 0.76–1.05 rad/mCi, respectively. These studies confirm the prolonged circulation and reduced immunogenicity of chimeric 17-1A versus murine 17-1A. Marrow radiation exposure using antibodies with prolonged circulation is a critical factor in planning for radioimmunotherapeutic applications.

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