Jun Yang1,2, Guang Zhang3,4, Qinqing Li1, Chengde Liao1, Lin Huang3,4, Tengfei Ke1, Huabei Jiang3,4,5, Dan Han2. 1. Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming 650118, Yunnan, China. 2. Department of Medical Imaging, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China. 3. School of Electronic Science and Engineering, University of Electronic Science and Technology, Chengdu 610054, China. 4. Center for Information in Biomedicine, University of Electronic Science and Technology, Chengdu 610054, China. 5. Department of Medical Engineering, University of South Florida, Tampa, FL 33620, USA.
Abstract
BACKGROUND: Photoacoustic imaging (PAI) provides real-time noninvasive and contrast agent-free monitoring of the concentrations of some endogenous compounds related to tumor vascularization and oxygenation. In this study, we used PAI to noninvasively evaluate tumor responses to antiangiogenic therapy. METHODS: In vivo studies were performed with the approval of our institutional animal ethics committee. We used a xenograft mouse model of 4T1 breast cancer treated with different doses of bevacizumab or vehicle. Seven days after implantation, tumor-bearing mice (with tumors ~5-8 mm diameter) were randomly divided into low-dose (10 mg/kg), high-dose (20 mg/kg) and vehicle groups (same dose of saline). Each experimental group was administered bevacizumab intraperitoneally only once. Before and after treatment, acoustic resolution-photoacoustic microscopy (AR-PAM), a type of PAI, was conducted in vivo consecutively from day 1 to day 5. PAI-derived quantitative parameters were calculated at each time point. Additional cohorts of mice were used to quantify CD31 and hypoxia by immunohistochemical assays. RESULTS: The values of the PAI parameters were not significantly different among the experimental and control groups at the same time point before treatment (all P>0.05). The total hemoglobin (HbT) levels in the treatment group gradually decreased from day 1 to day 2 (relative to those in the control group, P>0.05) and decreased significantly relative to those in the control group from day 3 to day 5 (P<0.05). The deoxyhemoglobin (HbR) levels in the treatment group decreased from day 1 to 5 after treatment. The high-dose group had significantly decreased HbR levels relative to the control group from day 1 to 5 (P<0.05). The low-dose group also showed a gradual and significant decrease in HbR levels on day 3 (P<0.05). CD31 was decreased in the low-dose group relative to the control group on day 1 (decreased by 34.05%, P=0.067) and day 3 (decreased by 45.27%, P=0.180), and the decrease in CD31 persisted on day 5 (decreased by 71.41%, P=0.000). CD31 decreased to a greater extent in the high-dose group than in the low-dose group. Tumor hypoxia was significantly increased on day 1 from day 0 in the treatment groups (P<0.05), especially in the high-dose group. Hypoxia was decreased on days 3 and 5 in the low-dose group (10.92±0.92 and 8.17±1.9, P=0.317) but continuously increased over time in the high-dose group. Significantly greater hypoxia was observed in the high-dose group than in the low-dose group (17.60±1.20 and 20.33±0.47, P<0.05). CONCLUSIONS: PAI can be used to evaluate both vessel regression and hypoxia in response to anti-vascular treatment.
BACKGROUND: Photoacoustic imaging (PAI) provides real-time noninvasive and contrast agent-free monitoring of the concentrations of some endogenous compounds related to tumor vascularization and oxygenation. In this study, we used PAI to noninvasively evaluate tumor responses to antiangiogenic therapy. METHODS: In vivo studies were performed with the approval of our institutional animal ethics committee. We used a xenograft mouse model of 4T1 breast cancer treated with different doses of bevacizumab or vehicle. Seven days after implantation, tumor-bearing mice (with tumors ~5-8 mm diameter) were randomly divided into low-dose (10 mg/kg), high-dose (20 mg/kg) and vehicle groups (same dose of saline). Each experimental group was administered bevacizumab intraperitoneally only once. Before and after treatment, acoustic resolution-photoacoustic microscopy (AR-PAM), a type of PAI, was conducted in vivo consecutively from day 1 to day 5. PAI-derived quantitative parameters were calculated at each time point. Additional cohorts of mice were used to quantify CD31 and hypoxia by immunohistochemical assays. RESULTS: The values of the PAI parameters were not significantly different among the experimental and control groups at the same time point before treatment (all P>0.05). The total hemoglobin (HbT) levels in the treatment group gradually decreased from day 1 to day 2 (relative to those in the control group, P>0.05) and decreased significantly relative to those in the control group from day 3 to day 5 (P<0.05). The deoxyhemoglobin (HbR) levels in the treatment group decreased from day 1 to 5 after treatment. The high-dose group had significantly decreased HbR levels relative to the control group from day 1 to 5 (P<0.05). The low-dose group also showed a gradual and significant decrease in HbR levels on day 3 (P<0.05). CD31 was decreased in the low-dose group relative to the control group on day 1 (decreased by 34.05%, P=0.067) and day 3 (decreased by 45.27%, P=0.180), and the decrease in CD31 persisted on day 5 (decreased by 71.41%, P=0.000). CD31 decreased to a greater extent in the high-dose group than in the low-dose group. Tumor hypoxia was significantly increased on day 1 from day 0 in the treatment groups (P<0.05), especially in the high-dose group. Hypoxia was decreased on days 3 and 5 in the low-dose group (10.92±0.92 and 8.17±1.9, P=0.317) but continuously increased over time in the high-dose group. Significantly greater hypoxia was observed in the high-dose group than in the low-dose group (17.60±1.20 and 20.33±0.47, P<0.05). CONCLUSIONS: PAI can be used to evaluate both vessel regression and hypoxia in response to anti-vascular treatment.
Authors: Poorva Ghosh; Yihang Guo; Adnin Ashrafi; Jingyu Chen; Sanchareeka Dey; Shigen Zhong; Jie Liu; James Campbell; Purna Chaitanya Konduri; Jeni Gerberich; Massoud Garrossian; Ralph P Mason; Li Zhang; Li Liu Journal: Cancer Res Date: 2020-06-16 Impact factor: 12.701