Radiation Biology

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SU_42_2419 - Dual Modality Shortwave Infrared Fluorescence and Photoacoutic Imaging of Radiation-Induced Vascular Damage in Stereotactic Ablative Radiation Therapy

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Dual Modality Shortwave Infrared Fluorescence and Photoacoutic Imaging of Radiation-Induced Vascular Damage in Stereotactic Ablative Radiation Therapy
K. Cheng1, F. Han1,2, G. Zhang3, W. Zhao4, C. H. Jenkins5, D. Vernekohl6, and L. Xing7; 1Stanford University, Radiation Oncology, Stanford, CA, 2State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Department of Radiation Oncology, Guangzhou, CA, China, 3School of Computer and Information Technology, Beijing Jiaotong University,, Beijing 100044, China, 4Stanford University, Palo Alto, CA, 5Department of Radiation Oncology, Stanford University, Stanford, CA, 6Stanford University, Stanford, CA, 7Stanford University School of Medicine, Palo Alto, CA

Purpose/Objective(s): The vascular damage plays an important role in the response of tumors to high-dose hypofractionated radiation such as stereotactic body radiotherapy (SBRT). Non-invasive diagnostic imaging is an essential element in the evaluation and quantification of radiation-induced vascular damage in tumors. The primary aim of our study was to assess the potential of a combination of two novel imaging modalities together (the fluorescence imaging in the second near-infrared window (NIR-II, 1000 - 1700 nm) and photoacoustic (PA) imaging) for direct morphological and functional measurement of the head and neck tumors response to SBRT.

Materials/Methods: Novel donor-acceptor chromophore-based nanoprobes (DAPs) with an absorption in NIR-I window and a fluorescence peak in NIR-II region were developed as contrast agents for both PA and NIR-II imaging in this study. We used a xenograft mouse model of human head & neck squamous carcinoma (SAS). Radiation therapy was performed using a 225 kVp image-guided small animal cabinet X-ray irradiator. The mice for conventional radiation therapy (CRT) were irradiated with 20 Gy in 5 fractions in 5 days, while the SBRT group was irradiated with 20 Gy in a single dose. Both PA and NIR-II imaging were performed one day before and 8 days after the radiation therapy after SAS tumor bearing mice were intravenously injected with DAPs.

Results: The DAPs show the unique ability to combine both PA and NIR-II modalities for tumor vasculature imaging. To repeatedly and non-invasively imaging the tumor area, we developed the principal component analysis (PCA) method to analyze the dynamic contrast enhanced images to differentiate the neovasculature from normal blood vessels and monitor the functional abnormalities of blood vessels. In the SAS tumors treated with CRT, the morphology and function of the vasculature was preserved during the treatment, but the irradiation with SBRT dramatically induced severe vascular damage to the tumors. The morphology and density of tumor blood vessels were evaluated using PA and NIR imaging. The result confirmed that severe vascular damage resulted in reduced blood perfusion. Although inhibition of tumor growth after CRT was observed, the regrowth of irradiated tumors appeared to be followed by neovascularization. There was a significant correlation between the extent of vascular density and survival rate of tumor mice.

Conclusion: Our study provided a direct proof that the tumor vessel density is related to underlying effects of SBRT. To the best of our knowledge, it is the first time to use dual PA and NIR-II imaging modalities to evaluate the responses of blood vessels to SBRT. Noninvasive measures of vessel density and function using PA and NIR-II imaging successfully detected vascular damage, which plays a critical role in the response of tumors to SBRT. With advances of dual modality imaging technology and availability of imaging probes, our approach could enable optimal scheduling of radiation therapy with improved therapeutic outcome.

Author Disclosure: K. Cheng: None. F. Han: None. W. Zhao: None. C.H. Jenkins: None. L. Xing: Research Grant; Varian Medical Systems. Honoraria; Varian Medical Systems. Royalty; Varian Medical Systems, Standard Imaging Inc.

Kai Cheng, PhD

Stanford University School of Medicine

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