Room: Exhibit Hall | Forum 4
Purpose: The development of radio-immunotherapy has cast the use of radiotherapy(RT) into a pivotal role in the management of pancreatic cancer. There is a need to establish a clinically-relevant experimental system to advance our understanding of RT. Most promising is the use of genetically engineered mouse models(GEMMs) that spontaneously develop pancreatic ductal adenocarcinoma(PDAC). As for the important pre-clinical research to study treatment response of this PDAC-GEMM, the research setting needs to mimic the RT used for human. Such technology is available in the form of small animal radiation research platform(SARRP). Recognizing that CBCT imaging is inadequate for localizing the PDAC growing in a low image contrast environment, we innovated bioluminescence tomography(BLT) to guide SARRP irradiation for in vivo bioluminescent PDAC and assess treatment response.
Methods: Multi-projection and multi-spectral BLT is established. We will first proceed with numerical mouse with segmented organs, which allows us optimize the parameters of optical properties and demonstrate the feasibility of BLT for abdominal target localization. For the in vivo radiation study, we will contour the BLT-derived PDAC volume in a pancreas specific inducible Kras-Twist1-Luc(bioluminescent) PDAC-GEMM. To account for the target localization uncertainty of the BLT-SARRP system, a margin will be added to the target volume. We will irradiate the contoured PDAC volume with conformal delivery at single dose of 10 Gy, confirmed by pathological staining.
Results: The inducible Kras-Twist1-Luc(bioluminescent) PDAC-GEMM is shown in Figure 1 and 2. The capability of our BLT-SARRP(Figure 3) retrieving tumor volume is demonstrated in an in vivo GBM model(Figure 4). These supporting data demonstrate the potentiality of using BLT to guide conformal irradiation for in vivo PDAC.
Conclusion: Our Kras-Twist1-Luc PDAC-GEMM and the CBCT-BLT-guided SARRP establish a novel experimental system that will enable researchers to develop new treatment options for human PDAC in ways that have not been feasible before.