Imaging of hypoxia in human glioblastoma with dynamic 18F-fluoromisonidazole PET

Abstract

Aim: The purpose of this study was to locate the levels of hypoxia in glioblastoma PET images measured with 18F-fluoromisonidazole in human subjects. It is recognized that tumors with hypoxia are resistant to treatment by radiotherapy and chemotherapy.

Methods: The images were acquired in dynamic mode for 15 min or 30 min and in static mode for two single scans at 2 h and 3 h to allow the accumulation of the radiotracer in the tumor. The images were analyzed at the voxel basis with compartmental analysis (CA) and with the usual tumor-to-blood uptake ratio (TBR). Kmeans algorithm was applied to cluster the levels of hypoxia in the images.

Results: TBR at a threshold of 1.2 at imaging times of 15 min, 2 h and 3 h produced images with different clusters. Also, the comparison of TBR with the distribution volume obtained with CA had a similarity index of 0.61 ± 0.05.

Conclusion: We found some differences in defining the hypoxic volume within a tumor using TBR. The compartmental analysis allowed discrimination of the tumor hypoxic sub-volumes which can be useful for a better treatment with radiotherapy.

Keywords

PET / 18F-fluoromisonidazole / glioblastoma / hypoxia / tumor-to-blood uptake ratio / compartmental modeling

References

[1] Gilbert MR.Recurrent glioblastoma: a fresh look at current therapies and emerging novel approaches..Semin Oncol2011;38:S21-33

[2] Vaupel P,Höckel M.Oxygen status of malignant tumors: pathogenesis of hypoxia and significance for tumor therapy..Semin Oncol2001;28:29-35

[3] Oliver L,Marhuenda F,Vallette F.Hypoxia and the malignant glioma microenvironment: regulation and implications for therapy..Curr Mol Pharmacol2009;2:263-84

[4] Comerford KM,Karhausen J,Montalto MC.Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance MDR1 gene..Cancer Res2002;62:3387-94

[5] Weeks AJ,Marsden PK,Lloyd DR.Radiobiological effects of hypoxia-dependent uptake of 64 Cu-ATSM: enhanced DNA damage and cytotoxicity in hypoxic cells..Eur J Nucl Med Mol Imaging2010;37:330-8

[6] Ling CC,Larson S,Fuks Z.Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality..Int J Radiat Oncol Biol Phys2000;47:551-60

[7] Hirata K,Shiga T,Magota K.18F-fluoromisonidazole positron emission tomography may differentiate glioblastoma multiforme from less malignant gliomas..Eur J Nucl Med Mol Imaging2012;39:760-70

[8] Miyake K,Okada M,Tamiya T.Usefulness of positron emission tomographic studies for gliomas..Neurol Med Chir (Tokyo)2016;56:396-408 PMCID:PMC4945598

[9] Fleming IN,Blower PJ,Williams KJ.Imaging tumour hypoxia with positron emission tomography..Br J Cancer2015;112:238-50 PMCID:PMC4453462

[10] Sokoloff L,Kennedy C,Patlak CS.The [14C] deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat..J Neurochem1977;28:897-916

[11] Li F,Hansen AE.Kinetic modeling in PET imaging of hypoxia..Am J Nucl Med Mol Imaging.2014;4:490-506 PMCID:PMC4171837

[12] Lim JL.An efficient radiosynthesis of [18F]fluoromisonidazole..Appl Radiat Isot1993;44:1085-91

[13] Phelps ME,Hoffman EJ,Sokoloff L.Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method..Ann Neurol1979;6:371-88

[14] Bruehlmeier M,Schubiger PA.Assessment of hypoxia and perfusion in human brain tumors using PET with 18F-fluoromisonidazole and 15O-H2O..J Nucl Med2004;45:1851-9

[15] McGowan DR,Papiez BW,Gleeson FV.Whole tumor kinetics analysis of 18F-fluoromisonidazole dynamic PET scans of non-small cell lung cancer patients, and correlations with perfusion CT blood flow..EJNMMI Res2018;8:73 PMCID:PMC6070455

[16] Bholowalia P.Ebk-means: a clustering technique based on elbow method and K-Means in WSN..Int J Comput Appl2014:105

[17] Wang Z,Sheikh HR.Image quality assessment: From error visibility to structural similarity..IEEE Trans Image Process2004;13:600-12

[18] Syakur MA,Rochman EMS.Integration K-means clustering method and elbow method for identification of the best customer profile cluster..IOP Conference Series: Materials Science and Engineering2018;

[19] Thorwarth D,Paulsen F.A kinetic model for dynamic [18F]-Fmiso PET data to analyse tumour hypoxia..Phys Med Biol2005;50:2209-24

[20] Dirix P,De Keyzer F,Hermans R.Dose painting in radiotherapy for head and neck squamous cell carcinoma: value of repeated functional imaging with 18F-FDG PET, 18F-fluoromisonidazole PET, diffusion-weighted MRI, and dynamic contrast-enhanced MRI..J Nucl Med2009;50:1020-7

[21] Zips D,Abolmaali N,Abramyuk A.Exploratory prospective trial of hypoxia-specific PET imaging during radiochemotherapy in patients with locally advanced head-and-neck cancer..Radiother Oncol2012;105:21-8