Contrast-enhanced MR imaging assessment of tumor capillary permeability: Effect of irradiation on delivery of chemotherapy

PURPOSE: To assess the effect of x rays on tumor capillary permeability with macromolecular contrast medium (MMCM)-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS: One of paired R3230 mammary adenocarcinomas implanted in the flanks of 48 Fischer rats was treated with a single 5- or 15-Gy dose of x rays. After 1 or 3 days, MR imaging in 30 rats was performed unenhanced and enhanced with albumin-(gadolinium diethylenetriaminepent aacetic acid)(30) (0.02 mmol gadolinium per kilogram body weight). Signal intensity enhancement was analyzed to estimate fractional blood volume and permeability-surface area product (PS). In 18 irradiated rats, 2.5 mg/kg cisplatin was injected intravenously, and fractional tumor platinum concentrations were measured spectrometrically. RESULTS: MR imaging showed highest capillary permeability 1 day after 15 Gy (PS 110% above control [P <.001]); PS was elevated 57% 1 day after 5 Gy and 63% 3 days after 15 Gy (P <.05). The largest mean tumor platinum fraction occurred 1 day after 15 Gy: 48% versus 20% (control) (P <.05). CONCLUSION: Transient irradiation-induced increase in tumor capillary permeability to cisplatin can be quantified with MMCM-enhanced MR imaging.