A Method to Quantitatively Measure Transcapillary Transport of Iodinated Compounds in Canine Brain Tumors with Computed Tomography

Abstract

We present a quantitative method for determining a blood-to-tissue influx constant (K₁), a tissue-to-blood efflux constant (k₂), and tissue plasma vascular space (V_p) that uses a computed tomographic (CT) scanner to make tissue and plasma measurements of the concentration of an iodinated compound. Meglumine iothalamate was infused intravenously over time periods of 0.5–5 min, up to 49 CT scans were obtained at one brain level, and arterial plasma was sampled over a 30- to 40-min period. K₁, k₂, and V_p were calculated for each voxel of the 320 × 320 matrix, using a two-compartment pharmacokinetic model and nonlinear least-squares regression. The method was used in dogs with avian sarcoma virus–induced brain tumors. As many as four studies on different days were done in the same animal. In tumor-free cortex, K₁ of meglumine iothalamate was 2.4 ± 1.7 μl g⁻¹ min⁻¹ (mean ± SD) and V_p was 3.4 ± 0.5 ml 100 g⁻¹. Mean whole-brain tumor K₁ values ranged from 3.3 to 97.9 μl g⁻¹ min⁻¹; k₂ ranged from 0.032 to 0.27 min⁻¹; and V_p ranged from 1.1 to 11.4 ml 100 g⁻¹. These values were reproducible in serial experiments in single animals. Independent verification of K₁ values was obtained with quantitative autoradiographic measurements of α-aminoisobutyric acid, which has similar physicochemical properties to meglumine iothalamate. The CT methodology is capable of demonstrating regional variation of trans-capillary transport in brain tumors and may be of value in the study of human brain tumors.