title: Characterization of hypoxia in malignant pleural mesothelioma with FMISO PET-CT.
abstract: OBJECTIVE
  Malignant pleural mesothelioma (MPM) is a chemotherapy resistant tumor with a poor prognosis. Hypoxia is increasingly recognized as an important factor in tumor aggressiveness and cellular resistance to chemotherapy and radiation treatment. This prospective pilot study was performed with [F-18] fluoromisonidazole (FMISO) PET-CT to characterize hypoxia in patients with MPM.
  
  
  METHODS
  Twenty prospectively recruited patients with histologically or cytologically confirmed MPM not currently receiving systemic or local treatment underwent both FMISO and fluorodeoxyglucose (FDG) PET-CT scans within 2 weeks. FMISO and FDG PET-CT scans were independently analyzed visually and semi-quantitatively using SUVmax and tumor to background ratio (TBR) in order to assess tumor hypoxia and metabolic activity. Lesion by lesion analysis was performed in sites of measurable pleural masses.
  
  
  RESULTS
  Visual analysis demonstrated tumor FMISO activity in 17 of 20 patients, and tumor FDG activity in 19 of 20 patients. Focal areas of bulky tumor were most likely to demonstrate hypoxia. In 19 patients suitable for semi-quantitative analysis the median FDG SUVmax was 6.4 (range 1.9-19.1), median FMISO SUVmax was 2.5 (range 1.4-3.7) and median FMISO TBR was 1.8 (1.1-2.5). There was a positive correlation between intensity of metabolic activity and hypoxia (r=0.72, p=0.001). Lesion by lesion analysis demonstrated a positive correlation between tumor thickness and FMISO activity (r=0.77, p<0.001).
  
  
  CONCLUSIONS
  This pilot study confirms that MPM is a tumor with significant areas of hypoxia, particularly in dominant tumor masses. The relationship of tumor hypoxia to effectiveness of chemotherapy and/or radiation therapy warrants prospective assessment.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Crawley 6009 & Department of Nuclear Medicine/WA PET Service, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia. Electronic address: roslyn.francis@uwa.edu.au.
authors.forename: Roslyn J
authors.initials: RJ
authors.lastname: Francis
authors.affiliation: Department of Nuclear Medicine/WA PET Service, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Segard
authors.affiliation: RAPID labs, Medical Technology and Physics, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia.
authors.forename: Laurence
authors.initials: L
authors.lastname: Morandeau
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Crawley 6009 & Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia.
authors.forename: Y C Gary
authors.initials: YC
authors.lastname: Lee
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Crawley 6009 & Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Millward
authors.affiliation: PathWest, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: Segal
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Crawley 6009 & Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Nowak
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015687:Cell Hypoxia / Q000502:physiology; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000032:analysis*; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000032:analysis; D010865:Pilot Projects; D010997:Pleural Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods; D011379:Prognosis; D011446:Prospective Studies; D019275:Radiopharmaceuticals / Q000032:analysis*; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D019788:Fluorodeoxyglucose F18; D008920:Misonidazole
keywords: Hypoxia; Mesothelioma; PET