title: Determination of the unmetabolised (18)F-FDG fraction by using an extension of simplified kinetic analysis method: clinical evaluation in paragangliomas.
abstract: Tumours with high (18)F-FDG uptake values on static late PET images do not always exhibit high proliferation indices. These discrepancies might be related to high proportion of unmetabolised (18)F-FDG components in the tissues. We propose a method that enables to calculate different (18)F-FDG kinetic parameters based on a new mathematical approach that integrates a measurement error model. Six patients with diagnosed non-metastatic paragangliomas (PGLs) and six control patients with different types of lesions were investigated in this pilot study using (18)F-FDG PET/CT. In all cases, a whole-body acquisition was followed by four static acquisitions centred over the target lesions, associated with venous blood samplings. We used an extension of the Hunter's method to calculate the net influx rate constant (K H). The exact net influx rate constant and vascular volume fraction (K i and V, respectively) were subsequently obtained by the method of least squares. Next, we calculated the mean percentages of metabolised (PM) and unmetabolised (PUM) (18)F-FDG components, and the times required to reach 80 % of the amount of metabolised (18)F-FDG (T80%). A test-retest evaluation indicated that the repeatability of our approach was accurate; the coefficients of variation were below 2 % regardless of the kinetic parameters considered. We observed that the PGLs were characterised by high dispersions of the maximum standardised uptake value SUVmax (9.7 ± 11, coefficient of variation CV = 114 %), K i (0.0137 ± 0.0119, CV = 87 %), and V (0.292 ± 0.306, CV = 105 %) values. The PGLs were associated with higher PUM (p = 0.02) and T80% (p = 0.02) values and lower k 3 (p = 0.02) values compared to the malignant lesions despite the similar SUVmax values (p = 0.55). The estimations of these new kinetic parameters are more accurate than SUVmax or K i for in vivo metabolic assessment of PGLs at the molecular level.
authors.affiliation: Department of Pharmacokinetics, UMR INSERM 911 CRO2, SMARTc, Faculty of Medicine-Pharmacy, Aix-Marseille University, 27, Boulevard Jean Moulin, 13385, Marseille Cedex 5, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Barbolosi
authors.affiliation: Department of Nuclear Medicine, Centre Henri Becquerel and Rouen University Hospital, Rouen, France.|QuantIF-LITIS, EA 4108, Rouen University, 1 rue d'Amiens, 76038, Rouen Cedex, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Hapdey
authors.affiliation: Department of Pharmacokinetics, UMR INSERM 911 CRO2, SMARTc, Faculty of Medicine-Pharmacy, Aix-Marseille University, 27, Boulevard Jean Moulin, 13385, Marseille Cedex 5, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Battini
authors.affiliation: Department of Pharmacokinetics, UMR INSERM 911 CRO2, SMARTc, Faculty of Medicine-Pharmacy, Aix-Marseille University, 27, Boulevard Jean Moulin, 13385, Marseille Cedex 5, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Faivre
authors.affiliation: Economics and Social Health and Medical Information Processing (SESSTIM, UMR912), Inserm, IRD, Aix-Marseille University, 13273, Marseille, France.|Public Health Department, APHM, La Timone University Hospital, 264 rue Saint-Pierre, 13385, Marseille Cedex 5, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Mancini
authors.affiliation: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver NICHD, NIH, Building 10, CRC, Room 1E-3140, 10 Center Drive MSC-1109, Bethesda, MD, 20892-1109, USA.
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
authors.affiliation: Department of Nuclear Medicine, La Timone University Hospital, European Center of Research in Medical Imaging (CERIMED), Aix-Marseille University, 264 rue Saint-Pierre, 13385, Marseille Cedex 5, France.
authors.forename: Bardia
authors.initials: B
authors.lastname: Farman-Ara
authors.affiliation: Department of Nuclear Medicine, La Timone University Hospital, European Center of Research in Medical Imaging (CERIMED), Aix-Marseille University, 264 rue Saint-Pierre, 13385, Marseille Cedex 5, France. david.taieb@ap-hm.fr.
authors.forename: David
authors.initials: D
authors.lastname: Taïeb
mesh_terms: D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D016022:Case-Control Studies; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D064847:Multimodal Imaging; D010235:Paraganglioma / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography; D014057:Tomography, X-Ray Computed
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: Mathematical modelling; Paraganglioma; Positron emission tomography; Radionuclide imaging