Abstract
Preclinical models of pancreatic ductal adenocarcinoma (PDAC) can greatly benefit from noninvasive imaging for evaluating disease progression and therapeutic response. Imaging approaches that can accurately and simultaneously track primary tumor growth, metastatic dissemination, and host cachexia over time are lacking. Herein, we report an optimized dual-contrast microCT protocol for longitudinal imaging in orthotopic murine models of PDAC. This method enables high-resolution, volumetric quantification of orthotopic primary tumors, liver and lung metastases, and paraspinal skeletal muscle, providing a dynamic view of both the tumor and host physiology. MicroCT primary tumor measurements were strongly correlated with endpoint tumor weights and outperformed 2D ultrasound in early detection and volumetric accuracy, particularly for small or irregularly shaped tumors. This platform revealed heterogeneous metastatic kinetics across PDAC models and uncovered an early, heterogeneous onset of skeletal muscle wasting, a hallmark of cancer cachexia. Notably, this protocol mimics clinical CT surveillance by enabling opportunistic cachexia assessment from tumor imaging datasets and offers substantial advantages over destructive endpoint analyses. Furthermore, microCT radiation dose had no effect on model endpoints. By capturing the temporal dynamics of tumor progression and host response, dual-contrast microCT serves as a powerful translational platform for preclinical PDAC research and therapeutic testing. SIGNIFICANCE: Dual-contrast microCT provides high-resolution, whole-body, noninvasive imaging in orthotopic murine PDAC models, enabling simultaneous tracking of tumor growth, metastasis, and skeletal muscle wasting, offering a clinically relevant, translational imaging platform.