title: 99mTc-NTP 15-5 Imaging for Cartilage Involvement in Experimental Rheumatoid Arthritis: Comparison with Routinely Used Molecular Imaging Methods and Sensitivity to Chronic Nonsteroidal Antiinflammatory Drug Treatment.
abstract: This study determined, using the intraarticular complete Freund adjuvant arthritis mice model, whether the radiotracer (99m)Tc-N-(triethylammonium)-3-propyl-[15]ane-N5 ((99m)Tc-NTP 15-5) targeting proteoglycans has a pathophysiologic validity for in vivo imaging of rheumatoid arthritis (RA) and its response to chronic nonsteroidal antiinflammatory drugs.
  
  
  METHODS
  We investigated the time course of cartilage remodeling by (99m)Tc-NTP 15-5 scintigraphy, bone damages by (99m)Tc-hydroxymethylene diphosphonate imaging, inflammation by (18)F-FDG PET, and joint proteoglycan content and pain behavior in animals, without and with meloxicam treatment. Paw circumference, thermal pain behavior, and histology as well as proteoglycan content of the whole joint were determined.
  
  
  RESULTS
  (99m)Tc-NTP 15-5 showed specific tracer accumulation within RA joints, with a significant increase in scintigraphic ratio observed in RA versus shams from day 3 to day 28. (18)F-FDG evidenced uptake in RA joints from day 15 to day 29. Animals treated with meloxicam (5 mg/kg) exhibited a dose-dependent decrease in both (99m)Tc-NTP 15-5 and (18)F-FDG uptake ratios versus saline-treated animals. (99m)Tc-hydroxymethylene diphosphonate bone scans were only positive at day 14 in RA versus shams, with a significant effect of meloxicam. An increase in proteoglycans of RA joint and thermal pain behavior were observed and were dose-dependently reduced by meloxicam.
  
  
  CONCLUSIONS
  These experimental results bring data in favor of the (99m)Tc-NTP 15-5 radiotracer for assessing, in vivo, cartilage remodeling in RA that could be used to monitor therapy.
authors.affiliation: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, Clermont-Ferrand, France INSERM, U 990, Clermont-Ferrand, France Clermont Université, Université d'Auvergne, Pharmacologie Fondamentale et Clinique de la Douleur, Clermont-Ferrand, France INSERM U1107 NEURO-DOL, Clermont-Ferrand, France; and.
authors.forename: Amit
authors.initials: A
authors.lastname: Khairnar
authors.affiliation: Clermont Université, Université d'Auvergne, Pharmacologie Fondamentale et Clinique de la Douleur, Clermont-Ferrand, France INSERM U1107 NEURO-DOL, Clermont-Ferrand, France; and.
authors.forename: Fabien
authors.initials: F
authors.lastname: Marchand
authors.affiliation: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, Clermont-Ferrand, France INSERM, U 990, Clermont-Ferrand, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Vidal
authors.affiliation: Clermont Université, Université d'Auvergne, Pharmacologie Fondamentale et Clinique de la Douleur, Clermont-Ferrand, France INSERM U1107 NEURO-DOL, Clermont-Ferrand, France; and.
authors.forename: Monique
authors.initials: M
authors.lastname: Etienne
authors.affiliation: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, Clermont-Ferrand, France INSERM, U 990, Clermont-Ferrand, France.
authors.forename: Imen
authors.initials: I
authors.lastname: Miladi
authors.affiliation: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, Clermont-Ferrand, France INSERM, U 990, Clermont-Ferrand, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Auzeloux
authors.affiliation: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, Clermont-Ferrand, France INSERM, U 990, Clermont-Ferrand, France CLCC Jean Perrin, Clermont-Ferrand, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Cachin
authors.affiliation: Clermont Université, Université d'Auvergne, Pharmacologie Fondamentale et Clinique de la Douleur, Clermont-Ferrand, France INSERM U1107 NEURO-DOL, Clermont-Ferrand, France; and.
authors.forename: Alain
authors.initials: A
authors.lastname: Eschalier
authors.affiliation: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, Clermont-Ferrand, France INSERM, U 990, Clermont-Ferrand, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Chezal
authors.affiliation: Clermont Université, Université d'Auvergne, Pharmacologie Fondamentale et Clinique de la Douleur, Clermont-Ferrand, France INSERM U1107 NEURO-DOL, Clermont-Ferrand, France; and.
authors.forename: Denis
authors.initials: D
authors.lastname: Ardid
authors.affiliation: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, Clermont-Ferrand, France INSERM, U 990, Clermont-Ferrand, France elisabeth.noirault@inserm.fr.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Miot-Noirault
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002356:Cartilage / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019788:Fluorodeoxyglucose F18; D006573:Heterocyclic Compounds, 1-Ring; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography; D011509:Proteoglycans / Q000378:metabolism; D000644:Quaternary Ammonium Compounds; D013667:Technetium
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006573:Heterocyclic Compounds, 1-Ring; C407019:N-(triethylammonium)-3-propyl(15)ane-N5; D011509:Proteoglycans; D000644:Quaternary Ammonium Compounds; D019788:Fluorodeoxyglucose F18; D013667:Technetium
keywords: 99mTc-NTP 15-5; proteoglycans; rheumatoid arthritis; scintigraphy