Pharmacokinetics, immune response, and biodistribution of iodine-131-labeled chimeric mouse/human IgG1,k 17-1A monoclonal antibody.
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.
Meredith
R F
RF
Department of Radiation Oncology, University of Alabama, Birmingham 35294.
LoBuglio
A F
AF
Plott
W E
WE
Orr
R A
RA
Brezovich
I A
IA
Russell
C D
CD
Harvey
E B
EB
Yester
M V
MV
Wagner
A J
AJ
Spencer
S A
SA
D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics*; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000556:secondary; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes