RATIONALE AND OBJECTIVES: To characterize the long-term effects of therapeutic doses of ionizing radiation on the uptake and distribution of percutaneously delivered particulate contrast media in normal lymph nodes. METHODS: Two milliliters of an iodinated nanoparticle suspension (76 mg I/mL) was injected subcutaneously or submucosally into nine normal adult beagles. Region of interest analysis was used to estimate the volume, attenuation, and iodine concentration of opacified targeted lymph nodes and nonopacifled contralateral nodes on 24-hour postinjection CT images. All lymph nodes were then irradiated with 50 Gy in 25 fractions of 2 Gy/d. Contrast-enhanced quantitative CT was repeated 12 months after irradiation. RESULTS: Contrast-enhanced nodes averaged 2.3+/-0.8 times the volume of nonenhanced contralateral nodes before irradiation. The mean attenuation of contrast-enhanced nodes increased to 305 to 380 Hounsfield units from a pre-enhancement value of approximately 25 Hounsfield units. Opacified node volumes after irradiation averaged 61% to 86% of preirradiation volumes but were generally not statistically different. Contrast uptake assessed by average attenuation and iodine concentration decreased significantly by an average of 17% to 22% after irradiation and was significantly less than preirradiation uptake. Qualitatively, irradiated nodes generally appeared smaller than nonirradiated nodes, but the distribution pattern of contrast media did not appear to be appreciably altered. CONCLUSIONS: Lymph node irradiation resulted in only minimal decreases in contrast media uptake and node volume at 12 months. These effects presumably would not appreciably alter the potential clinical value of indirect lymphography for evaluating patients undergoing radiation therapy.