Pharmacokinetics, immune response, and biodistribution of iodine-131-labeled chimeric mouse/human IgG1,k 17-1A monoclonal antibody.

Academic Article

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 greater than 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.
  • Published In

    Keywords

  • Adenocarcinoma, Adult, Aged, Antibodies, Monoclonal, Colonic Neoplasms, Female, Humans, Iodine Radioisotopes, Liver Neoplasms, Male, Middle Aged, Radionuclide Imaging, Tissue Distribution
  • Author List

  • Meredith RF; LoBuglio AF; Plott WE; Orr RA; Brezovich IA; Russell CD; Harvey EB; Yester MV; Wagner AJ; Spencer SA
  • Start Page

  • 1162
  • End Page

  • 1168
  • Volume

  • 32
  • Issue

  • 6