Room: Exhibit Hall | Forum 3
Purpose: To develop a multimodality imaging guided Small Animal Arc Radiation Treatment platform (iSMAART) for cancer imaging, radiotherapy guidance and treatment-response assessment, by integrating X-ray CT, bioluminescence tomography (BLT) and fluorescence molecular tomography (FMT) onboard a small animal irradiator.
Methods: CT is essential to provide anatomic information and electron density for radiation dose calculation. Using tumor-targeting molecular probes, BLT and FMT can achieve highly specific and sensitive imaging of tumors that cannot be discovered from CT. Moreover, because the bioluminescence and fluorescence signal can be directly related to the cancer cellular and molecular biomarker, BLT and FMT can be used to monitor tumor progress and assess treatment response. Multimodality BLT/CT imaging was conducted on mice respectively bearing orthotopic LNCaP and metastatic C4-2B prostate tumors stably expressing firefly luciferase. For multimodality FMT/CT imaging, we developed a novel fluorescent poly(lactic-co-glycolic) acid (PLGA) nanoparticle that was conjugated with anti-epidermal growth factor receptor (EGFR), to selectively target EGFR-overexpressing tumors. In vivo experiments were conducted on 7 mice (n=4 for PLGA-anti-EGFR group, n=3 for PLGA-IgG control group) for pharmacokinetics study. The mice were inoculated with 4T1 breast tumors overexpressing EGFR. Then FMT was performed to localize the tumors actively targeted with fluorescent PLGA nanoparticles, and to guide focal tumor radiation.
Results: BLT/FMT can accurately localize orthotopic tumors (with <0.5 mm localization error), recover tumor volume and guide radiation beam. Multicentric internal metastatic prostate tumors were clearly detected from BLT with high specificity. The active PLGA-anti-EGFR nanoparticle showed high targeting efficiency and long tumor retention (~1 week).
Conclusion: Using multimodality CT/BLT/FMT, iSMAART can provide complementary imaging information that accurately map the animal anatomy, sensitively detect tumors especially for metastatic tumors, precisely guide radiation and reliably assess treatment response. Combining tumor targeting nanoparticles, iSMAART can become a powerful tool in the study of targeted therapy.
Not Applicable / None Entered.