Technetium-99m-antiepidermal growth factor-receptor antibody in patients with tumors of epithelial origin: part II. Pharmacokinetics and clearances.

UNLABELLED: Radiolabeled antitumor antibodies hold promise for diagnostic imaging and therapy in oncology. The purpose of this study was to investigate the pharmacokinetics, clearances and possible differences of two dosage administrations of the 99mTc-labeled antiepidermal growth factor (EGF)-receptor antibody and to predict the best dose and schedule for future clinical evaluations of this radiopharmaceutical. METHODS: Nine patients (4 women, 5 men; mean age 46.4 +/- 14.0 yr) were administered 1-3 mg 99mTc-labeled anti-EGF-receptor antibody (a murine IgG2a isotype) by intravenous bolus infusion. After administration, blood samples were collected from 7 patients from an antecubital vein opposite to the injection side at intervals from 2 min to 24 hr after injection, and plasma samples were obtained for pharmacokinetic analysis. Appropriate plasma samples were examined for isotope clearance (i.e., microCi/ml at various intervals) and 99mTc complexation to plasma proteins by fast protein liquid chromatography (FPLC) analysis. Urine was collected from each patient at 3 hr intervals up to 24 hr after monoclonal antibody administration to monitor 99mTc clearance. Plasma time-activity curves were fitted to a two-compartment model using nonlinear least-squares regression analysis by the method of flexible polyhedrals. RESULTS: Plasma disappearance curves of 99mTc-labeled anti-EGF-receptor antibody were best fit by biexponential equation with a distribution half-life (t(1/2alpha)) of 0.137 +/- 0.076 hr (n = 7) and elimination half-life (t(1/2beta)) of 20.3 +/- 8.0 hr. Analysis of urine showed that activity clearance by this route amounted to 4.9% +/- 0.6% of the injected dose in 24 hr, and FPLC analysis showed no evidence of decomposition, only 6%-7% of 99mTc was in a low molecular weight species. CONCLUSION: Plasma pharmacokinetics and urine clearance indicate comparability in both doses. The pharmacokinetic properties of the 99mTc-labeled anti-EGF-receptor antibody were found to be dose-independent. These findings provide an initial characterization of the radiopharmaceutical disposition in patients and may be used as the basis for calculating a better estimate of biodistribution and dosimetry for patients who will receive 188Re-labeled anti-EGF-receptor antibody (MAb ior egf/r3) injection for radioimmunotherapy and warrants further controlled clinical trials to define the efficacy of the radiopharmaceutical.