Differential permeability and quantitative MR imaging of a human lung carcinoma brain xenograft in the nude rat

Abstract

This study characterized agent differential permeability, three-dimensional tumor volume, and survival in an LX-1 human small cell lung carcinoma intracerebral xenograft model in the nude rat. The percent accessible tissue space (distribution volume) and the permeability x capillary surface product for aminoisobutyric acid (M(r) 103), methotrexate (M(r) 454), dextran 10 (M(r) 10,000), and dextran 70 (M(r) 70,000) were measured between 8 and 16 days after inoculation of tumor. Magnetic resonance imaging and histology were used to quantitate intracerebral tumor volume (mm3). Accessible tissue space (ml/g) and permeability x capillary surface product in intracranial tumor, surrounding brain, and subcutaneous tumor decreased with increasing molecular weight of the agent, regardless of the number of days after inoculation. Accessible tissue space in intracranial tumor increased between 8 and 16 days for all agents except dextran 70. There was little change in the subcutaneous tumor or other tissues with time. Tumor volume calculations from imaging studies correlated with volumetric measurements from histological sections (r2 = 98.5%) and illustrated natural tumor progression (9 to 225 mm3). These results provide a basis for therapeutic design based on differential permeability of specific agents and the ability to quantitatively measure brain tumor volume for accessing tumor response.