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Early monitoring antiangiogenesis treatment response of Sunitinib in U87MG Tumor Xenograft by (18)F-FLT MicroPET/CT imaging.

ABSTRACT: It was aimed to monitor early treatment response of Sunitinib in U87MG models mimicking glioblastoma multiforme by longitudinal (18)F-FLT microPET/CT imaging in this study.U87MG tumor mice were intragastrically injected with Sunitinib at a dose of 80 mg/kg for consecutive 7 days. (18)F-FLT microPET/CT scans were acquired on days 0, 1, 3, 7, and 13 after therapy. Tumor sizes and body weight were measured. Tumor samples were collected for immunohistochemical analysis of proliferation and microvessel density (MVD) with anti-Ki67 and anti-CD31, respectively.The uptake ratios of tumor to the contralateral muscle (T/M) of (18)F-FLT in the Sunitinib group decreased from baseline to day 3 (T/M0 = 2.98 ± 0.33; T/M3 = 2.23 ± 0.36; P < 0.001), reached the bottom on day 7 (T/M7 = 1.96 ± 0.35; P < 0.001), and then recovered on day 13. The T/M of (18)F-FLT uptake in the control group remained around 3.0. There was no difference for the tumor size between both groups until day 11. (18)F-FLT uptakes of tumor were correlated with Ki67 staining index and MVD.Early therapy response to Sunitinib could be predicted via (18)F-FLT PET, which will contribute to monitoring antiangiogenesis treatment.

SUBMITTER: Bao X

PROVIDER: S-EPMC4000939 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Early monitoring antiangiogenesis treatment response of Sunitinib in U87MG Tumor Xenograft by (18)F-FLT MicroPET/CT imaging.

Bao Xiao X Wang Ming-Wei MW Zhang Yong-Ping YP Zhang Ying-Jian YJ

BioMed research international 20140409

<h4>Aim</h4>It was aimed to monitor early treatment response of Sunitinib in U87MG models mimicking glioblastoma multiforme by longitudinal (18)F-FLT microPET/CT imaging in this study.<h4>Methods</h4>U87MG tumor mice were intragastrically injected with Sunitinib at a dose of 80 mg/kg for consecutive 7 days. (18)F-FLT microPET/CT scans were acquired on days 0, 1, 3, 7, and 13 after therapy. Tumor sizes and body weight were measured. Tumor samples were collected for immunohistochemical analysis of ...[more]

PMID: 24860813

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Project description:PurposeCyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with endocrine-therapy have emerged as an important regimen of care for estrogen receptor (ER)-positive metastatic breast cancer, although identifying predictive biomarkers remains a challenge. We assessed the ability of two PET-proliferation tracers, [18F]FLT and [18F]ISO-1, for evaluating response to CDK4/6-inhibitor (palbociclib) and ER-antagonist (fulvestrant).Experimental designTo determine the effect of CDK4/6 inhibition combined with estrogen-blockade, we assessed cell proliferation in six breast cancer cell lines after 1, 3, and 6 days of treatment with palbociclib and/or fulvestrant. These data were correlated to in vitro radiotracer assays and results were verified by longitudinal [18F]FLT and [18F]ISO-1 micro-PET imaging performed in MCF7 tumor-bearing mice.ResultsAll palbociclib-sensitive cell lines showed decreased [18F]FLT accumulation and S-phase depletion after treatment, with both measures augmented by combination therapy. In contrast, these cells showed changes in [18F]ISO-1 analogue-binding and G0 arrest only after prolonged treatment. MicroPET imaging of MCF7 xenografts showed a significant decrease in [18F]FLT but no changes in [18F]ISO-1 uptake in all treated mice on day 3. On day 14, however, mice treated with combination therapy showed a significant decrease in [18F]ISO-1, corresponding to G0 arrest, while maintaining reduced [18F]FLT uptake, which corresponded to S-phase depletion.ConclusionsOur data suggest complementary roles of [18F]FLT and [18F]ISO-1 PET in evaluating tumor-proliferation after combined CDK4/6 inhibitor and endocrine therapy in breast cancer. [18F]FLT is more sensitive to immediate changes in S-phase, whereas [18F]ISO-1 can assess more delayed changes related to cell-cycle arrest and transition to G0 quiescence from combination therapy. These data suggest a potential role for early prediction of long-term response using these imaging biomarkers.

Project description:Background3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) has been used to evaluate tumor malignancy and cell proliferation in human brain gliomas. However, (18)F-FLT has several limitations in clinical use. Recently, (11)C-labeled thymidine analogue, 4'-[methyl-(11)C]thiothymidine ((11)C-4DST), became available as an in vivo cell proliferation positron emission tomography (PET) tracer. The present study was conducted to evaluate the usefulness of (11)C-4DST PET in the diagnosis of human brain gliomas by comparing with the images of (18)F-FLT PET.MethodsTwenty patients with primary and recurrent brain gliomas underwent (18)F-FLT and (11)C-4DST PET scans. The uptake values in the tumors were evaluated using the maximum standardized uptake value (SUVmax), the tumor-to-normal tissue uptake (T/N) ratio, and the tumor-to-blood uptake (T/B) ratio. These values were compared among different glioma grades. Correlation between the Ki-67 labeling index and the uptake values of (11)C-4DST and (18)F-FLT in the tumor was evaluated using linear regression analysis. The relationship between the individual (18)F-FLT and (11)C-4DST uptake values in the tumors was also examined.Results(11)C-4DST uptake was significantly higher than that of (18)F-FLT in the normal brain. The uptake values of (11)C-4DST in the tumor were similar to those of (18)F-FLT resulting in better visualization with (18)F-FLT. No significant differences in the uptake values of (18)F-FLT and (11)C-4DST were noted among different glioma grades. Linear regression analysis showed a significant correlation between the Ki-67 labeling index and the T/N ratio of (11)C-4DST (r = 0.50, P < 0.05) and (18)F-FLT (r = 0.50, P < 0.05). Significant correlations were also found between the Ki-67 labeling index and the T/B ratio of (11)C-4DST (r = 0.52, P < 0.05) and (18)F-FLT (r = 0.55, P < 0.05). A highly significant correlation was observed between the individual T/N ratio of (11)C-4DST and (18)F-FLT in the tumor (r = 0.79, P = 0.0001).ConclusionsThe present study demonstrates that (11)C-4DST is useful for the imaging of human brain gliomas with PET. A relatively higher background uptake of (11)C-4DST in the normal brain compared to (18)F-FLT limits the detection of low-tracer-uptake tumors. Moreover, no superiority was found in (11)C-4DST over (18)F-FLT in the evaluation of cell proliferation.

Dataset Information

Early monitoring antiangiogenesis treatment response of Sunitinib in U87MG Tumor Xenograft by (18)F-FLT MicroPET/CT imaging.

Publications

Early monitoring antiangiogenesis treatment response of Sunitinib in U87MG Tumor Xenograft by (18)F-FLT MicroPET/CT imaging.

Similar Datasets

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