Purpose: The developing radio-immunotherapy has cast radiation therapy(RT) into a pivotal role for pancreatic cancer. There is a need to study pancreatic cancer in pre-clinical setting to advance our understanding of RT. The challenge to study abdominal malignancy in vivo is lack of proper imaging guidance. Bioluminescence with its strong imaging contrast has been widely used to monitor tumor growth. We innovated bioluminescence tomography(BLT) to guide irradiation for orthotopic pancreatic ductal adenocarcinoma(PDAC), and monitor its growth and treatment response.
Methods: To establish orthotopic PDAC model, we implanted a fraction of BxPc3-Red-Fluc tumor into nude mouse pancreas. For BLT, mice were subject to multi-spectral multi-projection bioluminescence imaging(BLI), followed by small animal radiation research platform(SARRP) CBCT imaging. CBCT image was acquired to generate anatomical mesh for BLT reconstruction. We inserted a titanium wire to tumor center as a marker to validate BLT localization accuracy. We will also quantify the accuracy of BLT-reconstructed volume with MRI and ex vivo method. Volumetric bioluminescent power(BP), related to tumor viability, will also be assessed in comparing with surface BLI and ex vivo method, to determine if it is a proper metric for tumor monitoring and assessment. We will further irradiate orthotopic PDAC guided by BLT and demonstrate the application of BLT to longitudinally assess the change of PDAC volume/power in response to treatment.
Results: Our initial result shows BLT can retrieve the orthotopic PDAC location within 1.5mm accuracy at depth from 3-5mm, common depth observed in pancreatic study. The BP is observed linearly by 12-fold along with the tumor growth 4 weeks after tumor implanted. With BLT, we can reconstruct the 3D bioluminescent tumor volume using multiple-projection imaging.
Conclusion: The quantitative BLT system offers unique opportunities for researchers to study important pancreatic tumor in orthotopic setting to quantify its location, growth and response to therapeutic intervention.
Funding Support, Disclosures, and Conflict of Interest: The research was supported by National Institutes of Health/National Cancer Institute (R21CA223403, R37CA230341, and R01CA240811), and Cancer Prevention and Research Institute of Texas (RR200042). J. Wong receives royalty payment from a licensing agreement between Xstrahl Ltd. and Johns Hopkins University.
Optical Tomography, Image Guidance, Quantitative Imaging