CONTRIBUTIONS OF CELL KILL AND POSTTREATMENT TUMOR-GROWTH RATES TO THE REPOPULATION OF INTRACEREBRAL 9L TUMORS AFTER CHEMOTHERAPY - AN MRI STUDY

The drought of progress in clinical brain tumor therapy provides an im petus for developing new treatments as well as methods for testing the rapeutics in animal models. The inability of traditional assays to sim ultaneously measure tumor size, location, growth kinetics, and cell ki ll achieved by a treatment complicates the interpretation of therapy e xperiments in animal models. To address these issues, tumor volume mea surements obtained from serial magnetic resonance images were used to noninvasively estimate cell kill values in individual rats with intrac erebral 9L tumors after treatment with 0.5, 1, or 2 x LD10 doses of 1, 3-bis(2-chloroethyl)-1-nitrosourea. The calculated cell kill values We re consistently lower than those reported using traditional assays. A dose-dependent increase in 9L tumor doubling time after treatment was observed that significantly contributed to the time required for survi ving cells to repopulate the tumor mass. This study reveals that incre ases in animal survival are not exclusively attributable to the fracti on of tumor cells killed but rather are a function of the cell kill an d repopulation kinetics, both of which vary with treatment dose.