Combined use of (18)F-FDG and (18)F-FMISO in unresectable non-small cell lung cancer patients planned for radiotherapy: a dynamic PET/CT study.

Aim of this study was to evaluate and compare, by means of dynamic and static PET/CT, the distribution patterns and pharmacokinetics of fluorine-18 fluorodeoxyglucose ((18)F-FDG) and of fluorine-18-fluoromisonidazole ((18)F-FMISO) in non-small cell lung cancer (NSCLC) patients scheduled for intensity modulated radiation therapy (IMRT). Thirteen patients suffering from inoperable stage III NSCLC underwent PET/CTs with (18)F-FDG and (18)F-FMISO for tumor metabolism and hypoxia assessment accordingly. Evaluation of PET/CT studies was based on visual analysis, semi-quantitative (SUV) calculations and absolute quantitative estimations, after application of a two-tissue compartment model and a non-compartmental approach. (18)F-FDG PET/CT revealed all thirteen primary lung tumors as sites of increased (18)F-FDG uptake. Six patients demonstrated also in total 43 (18)F-FDG avid metastases; these patients were excluded from radiotherapy. (18)F-MISO PET/CT demonstrated 12/13 primary lung tumors with faint tracer uptake. Only one tumor was clearly (18)F-FMISO avid, (SUVaverage = 3.4, SUVmax = 5.0). Mean values for (18)F-FDG, as derived from dPET/CT data, were SUVaverage = 8.9, SUVmax = 15.1, K1 = 0.23, k2 = 0.53, k3 = 0.17, k4 = 0.02, influx = 0.05 and fractal dimension (FD) = 1.25 for the primary tumors. The respective values for (18)F-FMISO were SUVaverage = 1.4, SUVmax = 2.2, K1 = 0.26, k2 = 0.56, k3 = 0.06, k4 = 0.06, influx = 0.02 and FD = 1.14. No statistically significant correlation was observed between the two tracers. (18)F-FDG PET/CT changed therapy management in six patients, by excluding them from planned IMRT. (18)F-FMISO PET/CT revealed absence of significant tracer uptake in the majority of the (18)F-FDG avid NSCLCs. Lack of correlation between the two tracers' kinetics indicates that they reflect different molecular mechanisms and implies the discordance between increased glycolysis and hypoxia in the malignancy.

[1]  P. Vaupel,et al.  Hypoxia in cancer: significance and impact on clinical outcome , 2007, Cancer and Metastasis Reviews.

[2]  E. Graves,et al.  The tumor microenvironment in non-small-cell lung cancer. , 2010, Seminars in radiation oncology.

[3]  Gregor Sommer,et al.  Multimodal hypoxia imaging and intensity modulated radiation therapy for unresectable non-small-cell lung cancer: the HIL trial , 2012, Radiation oncology.

[4]  Daniela Thorwarth,et al.  Kinetic analysis of dynamic 18F-fluoromisonidazole PET correlates with radiation treatment outcome in head-and-neck cancer , 2005, BMC Cancer.

[5]  A. Nunn,et al.  Nitroimidazoles and imaging hypoxia , 1995, European Journal of Nuclear Medicine.

[6]  J. Fowler,et al.  A phase I/II radiation dose escalation study with concurrent chemotherapy for patients with inoperable stages I to III non-small-cell lung cancer: phase I results of RTOG 0117. , 2010, International journal of radiation oncology, biology, physics.

[7]  T. Momose,et al.  Noninvasive method to obtain input function for measuring tissue glucose utilization of thoracic and abdominal organs. , 1991, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[8]  R. Wahl,et al.  Influence of hypoxia on tracer accumulation in squamous-cell carcinoma: in vitro evaluation for PET imaging. , 1996, Nuclear medicine and biology.

[9]  C Burger,et al.  A JAVA environment for medical image data analysis: initial application for brain PET quantitation. , 1998, Medical informatics = Medecine et informatique.

[10]  D K Owens,et al.  Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. , 2001, JAMA.

[11]  D. Hose,et al.  PET/CT studies of multiple myeloma using 18 F-FDG and 18 F-NaF: comparison of distribution patterns and tracers’ pharmacokinetics , 2014, European Journal of Nuclear Medicine and Molecular Imaging.

[12]  Leyun Pan,et al.  Assessment of quantitative FDG PET data in primary colorectal tumours: which parameters are important with respect to tumour detection? , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[13]  H. Groen,et al.  Preoperative staging of non-small-cell lung cancer with positron-emission tomography. , 2000, The New England journal of medicine.

[14]  J. D. Chapman,et al.  Characteristics of the metabolism-induced binding of misonidazole to hypoxic mammalian cells. , 1983, Cancer research.

[15]  A. Scott,et al.  Hypoxia positron emission tomography imaging with 18f-fluoromisonidazole. , 2007, Seminars in nuclear medicine.

[16]  Leyun Pan,et al.  Quantitative approaches of dynamic FDG-PET and PET/CT studies (dPET/CT) for the evaluation of oncological patients , 2012, Cancer imaging : the official publication of the International Cancer Imaging Society.

[17]  Kunihiko Kobayashi,et al.  3) Non-small Cell Lung Cancer , 2012 .

[18]  John L. Humm,et al.  Pharmacokinetic Analysis of Hypoxia 18F-Fluoromisonidazole Dynamic PET in Head and Neck Cancer , 2010, Journal of Nuclear Medicine.

[19]  T W Griffin,et al.  Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole. , 1992, International journal of radiation oncology, biology, physics.

[20]  L G Strauss,et al.  The applications of PET in clinical oncology. , 1991, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[21]  A. Osmont,et al.  Determination of 18F-fluoro-2-deoxy-d-glucose rate constants in the anesthetized baboon brain with dynamic positron tomography , 1993, Journal of Neuroscience Methods.

[22]  Matthias Reimold,et al.  Prognostic impact of hypoxia imaging with 18F-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[23]  G. V. von Schulthess,et al.  Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography. , 2003, The New England journal of medicine.

[24]  K. Krohn,et al.  Radiolabelled fluoromisonidazole as an imaging agent for tumor hypoxia. , 1989, International journal of radiation oncology, biology, physics.

[25]  D. Townsend,et al.  Physical and clinical performance of the mCT time-of-flight PET/CT scanner , 2011, Physics in medicine and biology.

[26]  F. O’Sullivan,et al.  Hypoxia and Glucose Metabolism in Malignant Tumors , 2004, Clinical Cancer Research.

[27]  N. O'Rourke,et al.  Concurrent chemoradiotherapy in non-small cell lung cancer. , 2010, The Cochrane database of systematic reviews.

[28]  David L. Schwartz,et al.  Tumor Hypoxia Imaging with [F-18] Fluoromisonidazole Positron Emission Tomography in Head and Neck Cancer , 2006, Clinical Cancer Research.

[29]  W. Curran,et al.  Combined modality therapy for stage III non-small-cell lung cancer. , 2010, Seminars in radiation oncology.

[30]  M. Dewhirst,et al.  Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. , 1996, Cancer research.

[31]  Lester J. Peters,et al.  Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent , 2005, European Journal of Nuclear Medicine and Molecular Imaging.

[32]  Louis Sokoloff,et al.  Basic Principles Underlying Radioisotopic Methods for Assay of Biochemical Processes in Vivo , 1983 .

[33]  Y. Nishimura,et al.  A prospective clinical trial of tumor hypoxia imaging with 18 F-fluoromisonidazole positron emission tomography and computed tomography ( F-MISO PET / CT ) before and during radiation therapy , 2013 .

[34]  Alexandra L Hanlon,et al.  Hypoxic prostate/muscle pO2 ratio predicts for biochemical failure in patients with prostate cancer: preliminary findings. , 2002, Urology.

[35]  M. Eble,et al.  [18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography in response evaluation after chemo-/radiotherapy of non-small-cell lung cancer: a feasibility study , 2006, BMC Cancer.

[36]  A. Scott,et al.  Lack of correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in non-small cell lung cancer assessed by 18F-Fluoromisonidazole and 18F-FDG PET. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[37]  W. V. van Elmpt,et al.  Imaging techniques for tumour delineation and heterogeneity quantification of lung cancer: overview of current possibilities. , 2014, Journal of thoracic disease.

[38]  M. Boers,et al.  Effectiveness of positron emission tomography in the preoperative assessment of patients with suspected non-small-cell lung cancer: the PLUS multicentre randomised trial , 2002, The Lancet.

[39]  O. Brodin,et al.  Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials , 1995 .

[40]  C. Dooms,et al.  Positron-emission tomography in prognostic and therapeutic assessment of lung cancer: systematic review. , 2004, The Lancet. Oncology.

[41]  C Burger,et al.  Requirements and implementation of a flexible kinetic modeling tool. , 1997, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[42]  H. Groen,et al.  Hypoxia imaging using Positron Emission Tomography in non-small cell lung cancer: implications for radiotherapy. , 2012, Cancer treatment reviews.