Pharmacokinetics of indium-111-labeled B72.3 monoclonal antibody in colorectal cancer patients.
Mean time parameters provide a new approach to plasma pharmacokinetics of radiolabeled Mabs that may show important patient differences affecting diagnosis or treatment. We determined mean time pharmacokinetic parameters for 11 patients entered in a Phase I/II clinical trial for detection of colorectal cancer. Patients were administered 0.5-2 mg of B72.3 anti-TAG-72 radiolabeled with 3.5-5 mCi of 111In, plasma activity was measured over time. Mean time pharmacokinetic parameters were (mean +/- s.e.m.): mean residence time; body (MRTB) 88.9 +/- 7.2 hr, central (MRTC) 73.8 +/- 6.0 hr; mean transit time, central (MTTC) 41.1 +/- 9.0 hr; mean residence time, periphery (MRTP) 15.1 +/- 3.4 hr; intrinsic mean residence time, periphery (IMPTP) 39.0 +/- 7.6 hr; mean transit time, periphery (MTTP) 24.0 +/- 6.7 hr; probability of distribution (PRD) 50% +/- 10%; and n compartmental cycles of 4.54 +/- 2.3 times. In patients with increased circulating specific TAG-72 antigen, MRTC greater than MTTC and n much greater than 1. In patients without specific antigen, MRTC approximately equal to MTTC and n much less than 1. Pharmacokinetic studies may identify patients who do not have the tumor produced target antigen for the specific Mab and may provide an opportunity to select another specific Mab with an increased chance for successful diagnosis or treatment.
Webster
W B
WB
Department of Pharmacy, Bay Pines VA Medical Center, Florida.
Harwood
S J
SJ
Carroll
R G
RG
Morrissey
M A
MA
D000368:Aged; D000911:Antibodies, Monoclonal / Q000097:blood / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D004341:Drug Evaluation; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007205:Indium Radioisotopes; D008297:Male; D011877:Radionuclide Imaging
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006023:Glycoproteins; D007205:Indium Radioisotopes; C047052:tumor-associated antigen 72