Found programs:
Authors:Zhang Jinzhou; Shi Huimin; Zhang Liya; Miao Jingxuan; Zhu Gan; Zhao Xuefeng; Wang Hui
Keywords:dynamic whole-body PET/CT;Patlak;SUV ;MR ;combination therapy;abscopal effect
DOI:10.19405/j.cnki.issn1000-1492.2024.08.014
〔Abstract〕 Objective To monitor and evaluate the synergistic antitumor effects of programmed death-1(PD-1) checkpoint inhibitor combined with radiation therapy through whole-body dynamic18F-Fluorodeoxy glucose positron emission computed tomography(18F-FDG PET/CT) and Patlak multi-parametric analysis. Methods B16F10 melanoma dual-tumor mouse model was established and randomly divided into control, PD-1 monoclonal antibody, radiation-only, and combination groups(n=6). Whole-body18F-FDG PET/CT imaging was performed before and 24 hours post-treatment. The changes of maximum standardized uptake value(SUVmax) and metabolic rate of FDG(MRFDG) changes were analyzed and compared. Mice were then euthanized, tumors excised and underwent histopathology with HE, CD8, Ki-67 staining to assess immune infiltration and proliferation. Distal tumor volumes were monitored during treatment. Results At 24 hours post-treatment, in the primary tumors, SUVmaxand MRFDGvalues increased compared to pre-treatment in the control group(P<0.000 1), while they decreased in the combination treatment group(P<0.000 1), with statistically significant differences. In the distal tumors, SUVmaxand MRFDGvalues increased compared to pre-treatment in the control group, PD-1 monoclonal antibody group, and radiotherapy-alone group. The SUVmaxdifferences were statistically significant in the control group before and after treatment(P<0.000 1). MRFDGvalues in the distal tumors showed statistically significant differences in all three groups(P<0.01 orP<0.000 1). In the combination treatment group, SUVmaxand MRFDGvalues in the distal tumors decreased significantly compared to pre-treatment(P<0.000 1). Post-treatment comparison of SUVmaxand MRFDGvalues in the distal tumors showed that statistically significant differences in SUVmaxand MRFDGvalues were observed among all groups except between the radiotherapy-alone and PD-1 monoclonal antibody groups(allP<0.05). Immunohistochemistry results showed that the mean absorbance value of CD8 T lymphocytes in the distal tumor was significantly higher than that in the other three groups(P<0.001); the mean absorbance value of Ki-67 immunohistochemistry in the distal tumor proliferation index was significantly lower than that in the other three groups(P<0.001). Conclusion The synergistic effects of combined treatment reduced distal tumor growth. Whole-body18F-FDG PET/CT Patlak multi-parametric imaging can monitor the synergistic effects of PD-1 antibody and radiotherapy in B16F10 melanoma, providing reliable imaging parameters for optimizing combinatorial therapies.