DIFFERENTIAL PERMEABILITY AND QUANTITATIVE MR-IMAGING OF A HUMAN LUNG-CARCINOMA BRAIN XENOGRAFT IN THE NUDE RAT

This study characterized agent differential permeability, three-dimens ional tumor volume, and survival in an LX-I human small cell lung carc inoma intracerebral xenograft model in the nude rat. The percent acces sible tissue space (distribution volume) and the permeability x capill ary 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) wer e measured between 8 and 16 days after inoculation of tumor Magnetic r esonance imaging and histology were used to quantitate intracerebral t umor volume (mm(3)). Accessible tissue space (ml/g) and permeability x capillary surface product in intracranial tumor, surrounding brain, a nd subcutaneous tumor decreased with increasing molecular weight of th e agent, regardless of the number of days after inoculation. Accessibl e tissue space in intracranial tumor increased between 8 and IG days f or all agents except dextran 70. There was little change in the subcut aneous tumor or other tissues with time. Tumor volume calculations fro m imaging studies correlated with volumetric measurements from histolo gical sections (r(2) = 98.5%) and illustrated natural tumor progressio n (3 to 225 mm(3)). These results provide a basis for therapeutic desi gn based on differential permeability of specific agents and the abili ty to quantitatively measure brain tumor volume for accessing tumor re sponse.