Magnetic resonance imaging of response to chemotherapy in orthotopic xenografts of human bladder cancer.

Although orthotopic xenografts offer the potential for improved modeling of tumor development and response to therapy, noninvasive methods are not readily available to serially monitor tumors growing at internal sites in small rodents. In this study, magnetic resonance (MR) imaging techniques were developed using a clinical 1. 5 T whole body scanner to routinely monitor tumor growth kinetics of orthotopic UCRU-BL13 human bladder cancer xenografts after systemic chemotherapy. As a vehicle to test the system, comparisons were made between a standard agent, doxorubicin (DOX), and a novel formulation of liposome-encapsulated doxorubicin (DOXIL) to determine whether liposome encapsulation would alter chemosensitivity of BL13 in an orthotopic model. High resolution MR images acquired using direct three-dimensional data acquisitions yielded accurate volumetric measurements and detected tumors calculated to be </=10 mm3. MR volume measurements were comparable with tumor volumes calculated from direct caliper measurements. Both DOX and DOXIL demonstrated statistically significant therapeutic effect against orthotopic tumors; DOXIL reduced tumor volumes by approximately 33% (P < 0.005), whereas treatment with free DOX resulted in 70% reduction in tumor volume at termination (P < 0.002). We show that noninvasive MR assessments can be performed longitudinally to construct classical tumor growth curves, which can be used to evaluate therapeutic response in animal models. Translation of the MR techniques used in this study into clinical diagnostic evaluation would allow optimization of individual treatment schedules and facilitate assessment of therapeutic response.