title: Radiation treatment monitoring using multimodal functional imaging: PET/CT ((18)F-Fluoromisonidazole & (18)F-Fluorocholine) and DCE-US.
abstract: BACKGROUND
  This study aims to assess the effect of radiation treatment on the tumour vasculature and its downstream effects on hypoxia and choline metabolism using a multimodal approach in the murine prostate tumour model CWR22. Functional parameters derived from Positron Emission Tomography (PET)/Computer Tomography (CT) with (18)F-Fluoromisonidazole ((18)F-FMISO) and (18)F-Fluorocholine ((18)F-FCH) as well as Dynamic Contrast-Enhanced Ultrasound (DCE-US) were employed to determine the relationship between metabolic parameters and microvascular parameters that reflect the tumour microenvironment. Immunohistochemical analysis was employed for validation.
  
  
  METHODS
  PET/CT and DCE-US were acquired pre- and post-treatment, at day 0 and day 3, respectively. At day 1, radiation treatment was delivered as a single fraction of 10 Gy. Two experimental groups were tested for treatment response with (18)F-FMISO and (18)F-FCH.
  
  
  RESULTS
  The maximum Standardized Uptake Values (SUVmax) and the mean SUV (SUVmean) for the (18)F-FMISO group were decreased after treatment, and the SUVmean of the tumour-to-muscle ratio was correlated to microvessel density (MVD) at day 3. The kurtosis of the amplitude of the contrast uptake A was significantly decreased for the control tumours in the (18)F-FCH group. Furthermore, the eliminating rate constant of the contrast agent from the plasma k el derived from DCE-US was negatively correlated to the SUVmean of tumour-to-muscle ratio, necrosis and MVD.
  
  
  CONCLUSIONS
  The present study suggests that the multimodal approach using (18)F-FMISO PET/CT and DCE-US seems reliable in the assessment of both microvasculature and necrosis as validated by histology. Thus, it has valuable diagnostic and prognostic potential for early non-invasive evaluation of radiotherapy.
authors.affiliation: Department of Physics and Technology, University of Bergen, P.O. Box 7803, Bergen, 5020, Norway. Natalia.Arteaga@uib.no.
authors.forename: Natalia
authors.initials: N
authors.lastname: Arteaga-Marrero
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway. Cecilie.Rygh@uib.no.|Department of Health Sciences, Bergen University College, Bergen, Norway. Cecilie.Rygh@uib.no.
authors.forename: Cecilie
authors.initials: C
authors.lastname: Brekke Rygh
authors.affiliation: Department of Clinical Medicine, University of Bergen, Bergen, Norway. Jose.Gomez@uib.no.
authors.forename: Jose F
authors.initials: JF
authors.lastname: Mainou-Gomez
authors.affiliation: Department of Radiology, Haukeland University Hospital, Bergen, Norway. Tom.Adamsen@uib.no.|Department of Chemistry, University of Bergen, Bergen, Norway. Tom.Adamsen@uib.no.
authors.forename: Tom C H
authors.initials: TC
authors.lastname: Adamsen
authors.affiliation: Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, Lund, Sweden. nataliya.lutay@gmail.com.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Lutay
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway. Rolf.Reed@uib.no.|Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway. Rolf.Reed@uib.no.
authors.forename: Rolf K
authors.initials: RK
authors.lastname: Reed
authors.affiliation: Department of Physics and Technology, University of Bergen, P.O. Box 7803, Bergen, 5020, Norway. Dag.Rune.Olsen@uib.no.
authors.forename: Dag R
authors.initials: DR
authors.lastname: Olsen
mesh_terms: D000818:Animals; D002794:Choline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008920:Misonidazole / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008991:Monitoring, Physiologic; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D011878:Radiotherapy; D014057:Tomography, X-Ray Computed
chemical_list: C031843:fluoromisonidazole; C514960:fluorocholine; D008920:Misonidazole; D002794:Choline