Rapid and quantitative assessment of cancer treatment response using in vivo bioluminescence imaging

Current assessment of orthotopic tumor models in animals utilizes survival as the primary therapeutic end point. In vivo bioluminescence imaging (BLI) is a sensitive imaging modality that is rapid and accessible, and may comp rise an ideal tool for evaluating antineoplastic therapies [1]. Using human tumor cell lines constitutively expressing luciferase, the kinetics of tum or growth and response to therapy have been assessed in intraperitoneal [2] , subcutaneous, and intravascular [3] cancer models. However, use of this a pproach for evaluating orthotopic tumor models has not been demonstrated. I n this report, the ability of BLI to noninvasively quantitate the growth an d therapeutic-induced cell kill of orthotopic rat brain tumors derived from 9L gliosarcoma cells genetically engineered to stably express firefly luci ferase (9L(Luc)) was investigated. Intracerebral tumor burden was monitored over time by quantitation of photon emission and tumor volume using a cryo genically cooled CCD camera and magnetic resonance imaging (MRI), respectiv ely. There was excellent correlation (r=0.91) between detected photo ns and tu mor volume. A quantitative comparison of tumor cell kill determined fro m serial MRI volume measurements and BLI photon counts following 1,3-bis(2- chloroethyl)-1-nitrosourea (BCNU) treatment revealed that both imaging moda lities yielded statistically similar cell kill values (P=.951). These resul ts provide direct validation of BLI imaging as a powerful and quantitative tool for the assessment of antineoplastic therapies in living animals.