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Value of whole-body dynamic 18F-FMISO PET/CT Patlak multi-parameter imaging for evaluating the early radiosensitizing effect of oleanolic acid on C6 rat gliomas

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Abstract

The purpose of this study was to investigate the value of tumour-to-muscle (T/M) ratios and Patlak Ki images extracted from whole-body dynamic 18F-fluoromisonidazole (FMISO) PET/CT Patlak multi-parameter imaging for evaluating the early radiosensitizing effect of oleanolic acid (OA). Twenty-four rats with C6 gliomas were divided into 4 groups and treated with OA (group B), radiotherapy (group C), both (group D) or neither (group A). Whole-body dynamic 18F-FMISO PET/CT scans were performed for 120 min before treatment and 24 h following the treatment course. The tumour samples were dissected for hematoxylin and eosin staining, and HIF-1α, Ki-67 and GLUT-1 immunohistochemical staining. PET images were analysed using kinetic modelling (Patlak Ki) and static analysis (T/M ratios), and correlated with immunohistochemical results. The changes in T/M ratios, Ki values and tumour volume before treatment and 24 h following the treatment course were compared, and the survival time of tumour-bearing rats was recorded. Kaplan–Meier analysis showed that OA combined with radiotherapy can inhibit tumour growth and prolong the survival time of tumour-bearing rats. Whole-body dynamic 18F-FMISO PET/CT showed that the Ki values in group D were significantly lower than those in group C, whilst there was no significant difference in T/M ratios between groups C and D. The Pearson correlation coefficient analysis showed that Ki values were significantly related to immunohistochemical results. Our study suggests that Patlak Ki images may add value to PET/CT static images for evaluating the early radio-sensitizing effect of OA.

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Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

References

  1. Sui Z, Zhang X, Li H, Xu D, Li G (2021) Magnetic resonance imaging evaluation of brain glioma before postoperative radiotherapy. Clin Transl Oncol 23:820–826

    Article  CAS  Google Scholar 

  2. Clarke RH, Moosa S, Anzivino M, Wang Y, Floyd DH et al (2014) Sustained radiosensitization of hypoxic glioma cells after oxygen pretreatment in an animal model of glioblastoma and in vitro models of tumor hypoxia. PLoS ONE 9:e111199

    Article  Google Scholar 

  3. Toyonaga T, Hirata K, Shiga T, Nagara T (2017) Players of “hypoxia orchestra” - what is the role of FMISO? Eur J Nucl Med Mol Imaging 44:1679–1681

    Article  Google Scholar 

  4. Mudassar F, Shen H, O’Neill G, Hau E (2020) Targeting tumor hypoxia and mitochondrial metabolism with anti-parasitic drugs to improve radiation response in high-grade gliomas. J Exp Clin Cancer Res 39:208

    Article  CAS  Google Scholar 

  5. Hua L, Wang Z, Zhao L, Mao H, Wang G et al (2018) Hypoxia-responsive lipid-poly-(hypoxic radiosensitized polyprodrug) nanoparticles for glioma chemo- and radiotherapy. Theranostics 8:5088–5105

    Article  CAS  Google Scholar 

  6. Horsman MR, Mortensen LS, Petersen JB, Busk M, Overgaard J (2012) Imaging hypoxia to improve radiotherapy outcome. Nat Rev Clin Oncol 9:674–687

    Article  CAS  Google Scholar 

  7. Qi R, Jin W, Wang J, Yi Q, Yu M et al (2014) Oleanolic acid enhances the radiosensitivity of tumor cells under mimetic hypoxia through the reduction in intracellular GSH content and HIF-1alpha expression. Oncol Rep 31:2399–2406

    Article  CAS  Google Scholar 

  8. Gao D, Tang S, Tong Q (2012) Oleanolic acid liposomes with polyethylene glycol modification: promising antitumor drug delivery. Int J Nanomed 7:3517–3526

    Article  CAS  Google Scholar 

  9. Fahrni G, Karakatsanis NA, Di Domenicantonio G, Garibotto V, Zaidi H (2019) Does whole-body Patlak (18)F-FDG PET imaging improve lesion detectability in clinical oncology? Eur Radiol 29:4812–4821

    Article  Google Scholar 

  10. Cheebsumon P, Velasquez LM, Hoekstra CJ, Hayes W, Kloet RW et al (2011) Measuring response to therapy using FDG PET: semi-quantitative and full kinetic analysis. Eur J Nucl Med Mol Imaging 38:832–842

    Article  CAS  Google Scholar 

  11. Bartlett RM, Beattie BJ, Naryanan M, Georgi JC, Chen Q et al (2012) Image-guided PO2 probe measurements correlated with parametric images derived from 18F-fluoromisonidazole small-animal PET data in rats. J Nucl Med 53:1608–1615

    Article  CAS  Google Scholar 

  12. van der Weerdt AP, Klein LJ, Boellaard R, Visser CA, Visser FC et al (2001) Image-derived input functions for determination of MRGlu in cardiac (18)F-FDG PET scans. J Nucl Med 42:1622–1629

    Google Scholar 

  13. Freedman NM, Sundaram SK, Kurdziel K, Carrasquillo JA, Whatley M et al (2003) Comparison of SUV and Patlak slope for monitoring of cancer therapy using serial PET scans. Eur J Nucl Med Mol Imaging 30:46–53

    Article  Google Scholar 

  14. Ali MY, Oliva CR, Noman A, Allen BG, Goswami PC et al (2020) Radioresistance in glioblastoma and the development of radiosensitizers. Cancers (Basel) 12:2511

    Article  CAS  Google Scholar 

  15. Abdo RA, Lamare F, Fernandez P, Bentourkia M (2019) Analysis of hypoxia in human glioblastoma tumors with dynamic 18F-FMISO PET imaging. Australas Phys Eng Sci Med 42:981–993

    Article  Google Scholar 

  16. Chedeville AL, Madureira PA (2021) The role of hypoxia in glioblastoma radiotherapy resistance. Cancers (Basel) 13:542

    Article  CAS  Google Scholar 

  17. Gong L, Zhang Y, Liu C, Zhang M, Han S (2021) Application of radiosensitizers in cancer radiotherapy. Int J Nanomedicine 16:1083–1102

    Article  Google Scholar 

  18. Wang J, Yu M, Xiao L, Xu S, Yi Q et al (2013) Radiosensitizing effect of oleanolic acid on tumor cells through the inhibition of GSH synthesis in vitro. Oncol Rep 30:917–924

    Article  CAS  Google Scholar 

  19. Rahmim A, Lodge MA, Karakatsanis NA, Panin VY, Zhou Y et al (2019) Dynamic whole-body PET imaging: principles, potentials and applications. Eur J Nucl Med Mol Imaging 46:501–518

    Article  Google Scholar 

  20. van Sluis J, Yaqub M, Brouwers AH, Dierckx R, Noordzij W et al (2021) Use of population input functions for reduced scan duration whole-body Patlak (18)F-FDG PET imaging. EJNMMI Phys 8:11

    Article  Google Scholar 

  21. Karakatsanis NA, Zhou Y, Lodge MA, Casey ME, Wahl RL et al (2015) Generalized whole-body Patlak parametric imaging for enhanced quantification in clinical PET. Phys Med Bio 60:8643–8673

    Article  CAS  Google Scholar 

  22. Patlak CS, Blasberg RG (1983) Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 3:1–7

    Article  CAS  Google Scholar 

  23. Masaki Y, Shimizu Y, Yoshioka T, Nishijima KI, Zhao S et al (2017) FMISO accumulation in tumor is dependent on glutathione conjugation capacity in addition to hypoxic state. Ann Nucl Med 31:596–604

    Article  CAS  Google Scholar 

  24. Toyonaga T, Hirata K, Yamaguchi S, Hatanaka KC, Yuzawa S et al (2016) (18)F-fluoromisonidazole positron emission tomography can predict pathological necrosis of brain tumors. Eur J Nucl Med Mol Imaging 43:1469–1476

    Article  CAS  Google Scholar 

  25. Toyonaga T, Yamaguchi S, Hirata K, Kobayashi K, Manabe O et al (2017) Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor. Eur J Nucl Med Mol Imaging 44:611–619

    Article  CAS  Google Scholar 

  26. Eschmann SM, Paulsen F, Reimold M, Dittmann H, Welz S et al (2005) Prognostic impact of hypoxia imaging with 18F-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy. J Nucl Med 46:253–260

    Google Scholar 

  27. Gagel B, Piroth M, Pinkawa M, Reinartz P, Zimny M et al (2007) pO polarography, contrast enhanced color duplex sonography (CDS), [18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography: validated methods for the evaluation of therapy-relevant tumor oxygenation or only bricks in the puzzle of tumor hypoxia? BMC Cancer 7:113

    Article  Google Scholar 

  28. Jiang BH, Semenza GL, Bauer C, Marti HH (1996) Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension. Am J Physiol-Cell Ph 271:C1172–C1180

    Article  CAS  Google Scholar 

  29. Sun J, Chen C, Wei W, Zheng H, Yuan J et al (2015) Associations and indications of Ki67 expression with clinicopathological parameters and molecular subtypes in invasive breast cancer: a population-based study. Oncol Lett 10:1741–1748

    Article  CAS  Google Scholar 

  30. Takahashi M, Nojima H, Kuboki S, Horikoshi T, Yokota T et al (2020) Comparing prognostic factors of Glut-1 expression and maximum standardized uptake value by FDG-PET in patients with resectable pancreatic cancer. Pancreatology 20:1205–1212

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (No.81971643).

Funding

National Natural Science Foundation of China, no.81971643, Huiqin Xu.

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Contributions

HX conceived the experiments. KC and QZ conducted the experiments. KC analysed the data and drafted the manuscript. HX, HW, WY and YX revised the paper. All authors read and approved the final manuscript.

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Correspondence to Huiqin Xu.

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The authors declare that they have no competing interests.

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All experimental animal protocols were approved by the Ethics Review Committee for Animal Experimentation of Anhui Medical University.

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Cai, K., Zhang, Q., Wang, H. et al. Value of whole-body dynamic 18F-FMISO PET/CT Patlak multi-parameter imaging for evaluating the early radiosensitizing effect of oleanolic acid on C6 rat gliomas. Cancer Chemother Pharmacol 91, 133–141 (2023). https://doi.org/10.1007/s00280-022-04502-7

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