QUANTITATIVE MEASUREMENTS OF CAPILLARY TRANSPORT IN HUMAN BRAIN-TUMORS BY COMPUTED-TOMOGRAPHY

The rate at which water-soluble chemotherapeutic drugs enter brain tumors can be extremely variable. The ability to measure or predict the rate of drug entry may have an important role in treatment. We have developed a method that uses information from contrast-enhanced computed tomographic scans to measure quantitatively the rate of transcapillary transport of iodinated compounds in brain tumors. In a group of 10 patients with brain tumors, we obtained serial measurements of tissue (A(m)) and arterial plasma (C(p)) iodine concentration from timed computed tomographic scans done over 30 minutes, after intravenous infusion of meglumine iothalamate (Conray-60). These measurements were analyzed with a two-compartment pharmacokinetic model and nonlinear least-squares regression methods to obtain K1, a blood-to-tissue transfer constant; k2, a tissue-to-blood rate constant; and V(p), tissue plasma vascular volume. Images of K1, k2, and V(p) were reconstructed after calculating these values for each 0.8 x 0.8 x 5-mm volume element of the original data. Mean whole tumor K1 values varied from 2.0-mu-l gm-1 min-1 in a thalamic astrocytoma to 33.9-mu-1 gm-1 min-1 in a glioblastoma multiforme. The value of k2 varied from 0.034 to 0.108 min-1, and V(p) varied from 2.4 to 7.9 ml 100 gm-1. In tumor-free brain, the K1 of meglumine iothalamate was 2.9-mu-l gm-1 min-1; k2 was 0.058 min-1; and V(p) was 2.1 ml 100 gm-1. There was pronounced variability in transcapillary transport values between different malignant brain tumors, as well as regional variabilit within individual tumors, with focal increases in K1 up to 50-fold normal brain values. This approach provides a quantitative method to measure the rate of transcapillary transport of passively distributed iodinated compounds in human brain tumors. These types of measurements can be used to study serial changes of capillary permeability in individual patients that occur as a result of therapeutic manipulation and may, potentially, be used to individualize chemotherapy.