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 In-111, plasma activity was measured over time. Mean time pharmacokinetic parameters were (XBAR +/- s.e.m.): mean residence time; body (MRT(B)) 88.9 +/- 7.2 hr, central (MRT(C)) 73.8 +/- 6.0 hr; mean transit time, central (MTT(C)) 41.1 +/- 9.0 hr; mean residence time, periphery (MRT(P)) 15.1 +/- 3.4 hr; intrinsic mean residence time, periphery (IMPT(P)) 39.0 +/- 7.6 hr; mean transit time, periphery (MTT(P)) 24.0 +/- 6.7 hr; probability of distribution (PRD) 50% +/- 10%; and nBAR compartmental cycles of 4.54 +/- 2.3 times. In patients with increased circulating specific TAG-72 antigen, MRT(C) > MTT(C) and nBAR >> 1. In patients without specific antigen, MRT(C) congruent-to MTT(C) and nBAR << 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.