| Background and objective:To analyze the role of 18F-FDG PET-CT in predicting and judging the radiosensitivity of tumors. To study the correlations between hypoxia, angiogenesis, proliferation and the FDG standard uptake value of tumors.Methods:The BALB/c mice xenograft models of B16, CT26 and EMT6 cell lines were used for PET-CT scans when the tumors grew to 0.8-1cm. After the scans, five mice from every xenograft group were sacrificed randomly and the tumor specimens were harvested. The remaining fifteen mice of every group were divided into three groups. One group was sham irradiated with 6MV-X (control group); one group was irradiated with a dose of 3.5Gy/f×10f (low dose group); the other group was irradiated with a dose of 5Gy/f×10f. (high dose group). After the radiotherapy (RT), PET-CT scans were acquired again and all the mice were sacrificed and the tumor specimens were harvested for immunohistochemistry study. The T/NT value (the ratio of the max SUV of the tumor compared to that of contralateral normal muscle) was used to represent the tumor FDG uptake. The ratio of post-RT T/NT compared to pre-RT T/NT (T/N_ratio) represented the changes of the tumor FDG uptake during the RT. The ratio of the post-RT tumor volume compared to the pre-RT volume (V_ratio) reflected the early response of the tumor after RT. HIF-la, PCNA and microvessel density (MVD) immunohistochemical staining were carried out. CD31 antibody was used to mark vascular endothelial cell for the counting of microvessels. Results:The pre-RT T/NT values of the xenografts of B16, CT26 and EMT6 cell lines were 4.51±0.57,2.16±1.07 and 2.58±0.39 respectively. The T/NT value of the B16 xenograft was higher than that of the CT26 and EMT6 xenografts (P=0.029 and 0.001, respectively). But the difference between the latter two was not significant (P=0.437).After radiotherapy,①In the B16 xenografts, the T/N_ratio in the control group (2.56±1.70) was much higher than the low dose group (1.99±0.65, P=0.613) and the high dose group (1.60±0.72, P=0.415) respectively; and the V_ratio was higher in the control group (3.40±0.62) than in the low dose group (1.48±0.27, P=0.008) and the high dose group (1.06±1.00,P=0.003) respectively.②In the CT26 xenografts, the T/N_ratio in the control group was 0.86±0.16, which was higher than in the low dose group (0.64±0.25, P=0.272) and the high dose group (0.40±0.08, P=0.013) respectively; and the V_ratio in the control group was 5.37±3.35, which was higher than in the low dose group (0.86±0.11, P=0.142) and the high dose group (0.63±0.43, P=0.007) respectively.③In the EMT6 xenografts, the T/N_ratios in the control group was 0.11±0.01, compared with that in the low dose group (0.25±0.11, P=0.446) and high dose group (0.37±0.10, P=0.011); and the V_ratios were 4.78±0.98, compared with 1.15±0.27 (P=0.003) and 1.15±0.19 (P=0.003) respectively.Because tumor specimens of EMT6 were necrotic severely, we have not analyzed the immunohistochemical results.①Before radiotherapy, both the HIF-1a positive ratio and the PCNA positive ratio in the B16 xenografts were higher than in CT26 xenografts (P=0.039 and 0.047, respectively), the MVD in B16 was lower than in CT26 (P=0.007). The T/NT value was positively correlated with the HIF-1a positive ratio and the PCNA positive ratio both in the B16 and CT26 xenografts (r=0.765, P=0.045; r=0.772, P=0.042 for HIF1-a positive ratio; r=0.955, P=0.01; r=0.875, P=0.035 for PCNA positive ratio); but not with MVD in either of the two xenogragfts (r=-0.109, P=0.816 and r=0.418, P=0.351).②Compared to the pre-RT value, the presentation of HIF-1a and PCNA were all increased in the control group and in the RT groups in the B16 xenografts. However, in the CT26 xenograft groups, they were decreased in both of the RT groups but increased in the control group.Conclusion:1. Different radiosensitive tumors have different F-FDG uptake, suggesting pre-RT 18F-FDG PET-CT can preliminaryly predict the radiosensitivity of tumors.2. The 18F-FDG uptake of radiosensitive tumors decreased apparently and the delay of tumor growth is obvious, which suggesting that the change of FDG uptake during radiotherapy could be used to judge the radiosensitivity of tumors and instruct clinician to adjust further therapy.3. For the same kind of tumor, the change of FDG uptake may be different when different radiotherapy model and dose were administrated. Also, the change is correlated with the radiotherapy response. Therefore, we can adjust the radiotherapy plan accordingly to improve the treatment outcomes.4. The hypoxia and proliferation of tumors correlated with 18F-FDG uptake, which maybe contribute to the predicting power of 18F-FDG PET-CT scan.
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