Quantification of Tumor Location and Growth for Orthotopic Pancreatic Cancer Model Using Bioluminescence Tomography-Guided System

Abstract

<h3>Purpose/Objective(s)</h3> The developing radio-immunotherapy has cast the use of radiation therapy (RT) into a pivotal role in the management of pancreatic cancer. There is a need to study pancreatic cancer in pre-clinical setting to advance our understanding of the role 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 3D bioluminescence tomography (BLT) to guide irradiation for an orthotopic pancreatic ductal adenocarcinoma (PDAC), and monitor its growth and treatment response. <h3>Materials/Methods</h3> To establish the orthotopic PDAC model, we implanted a fraction of BxPc3-Red-FLuc tumor into the pancreas of a nude mouse. For BLT, mice were subject to multi-spectral and 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 the center of tumor as the marker to validate the BLT localization accuracy. We will also quantify the accuracy of BLT reconstructed volume with MRI and ex vivo method. Volume-averaged 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 the in vivo PDAC volume guided by BLT and demonstrate the application of BLT to longitudinally assess the change of PDAC volume/power in response to treatment. <h3>Results</h3> Our initial result shows 3D BLT can retrieve the orthotopic PDAC location within 1.5 mm accuracy at depth from 3-5 mm, common depth observed in pancreatic study. The BP is observed linearly by 12-fold along the tumor growth 4 weeks after tumor implantation. With BLT, we are able to reconstruct the 3D bioluminescent tumor volume using multiple-projection imaging. <h3>Conclusion</h3> 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.