title: 99mTc-NTP 15-5 assessment of the early therapeutic response of chondrosarcoma to zoledronic acid in the Swarm rat orthotopic model.
abstract: BACKGROUND
  Since proteoglycans (PGs) appear as key partners in chondrosarcoma biology, PG-targeted imaging using the radiotracer 99mTc-N-(triethylammonium)-3-propyl-[15]ane-N5 (99mTc-NTP 15-5) developed by our group was previously demonstrated to be a good single-photon emission computed tomography tracer for cartilage neoplasms. We therefore initiated this new preclinical study to evaluate the relevance of 99mTc-NTP 15-5 imaging for the in vivo monitoring and quantitative assessment of chondrosarcoma response to zoledronic acid (ZOL) in the Swarm rat orthotopic model.
  
  
  RESULTS
  Rats bearing chondrosarcoma in the orthotopic paratibial location were treated by ZOL (100 μg/kg, subcutaneously) or phosphate-buffered saline, twice a week, from day 4 to day 48 post-tumor implantation. 99mTc-NTP 15-5 imaging was performed at regular intervals with the target-to-background ratio (TBR) determined. Tumor volume was monitored using a calliper, and histology was performed at the end of the study. From day 11 to day 48, mean TBR values ranged from 1.7 ± 0.6 to 2.3 ± 0.6 in ZOL-treated rats and from 2.1 ± 1.0 to 4.9 ± 0.9 in controls. Tumor growth inhibition was evidenced using a calliper from day 24 and associated to a decrease in PG content in treated tumor tissues (confirmed by histology).
  
  
  CONCLUSIONS
  This work demonstrated two proofs of concept: (1) biphosphonate therapy could be a promising therapeutic approach for chondrosarcoma; (2) 99mTc-NTP 15-5 is expected to offer a novel imaging modality for the in vivo evaluation of the extracellular matrix features of chondrosarcoma, which could be useful for the follow-up and quantitative assessment of proteoglycan 'downregulation' associated to the response to therapeutic attempts.
authors.affiliation: INSERM UMR 990, Université d'Auvergne, BP 184, Rue Montalembert, Clermont-Ferrand, Cédex, 63005, France. elisabeth.noirault@inserm.fr.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Miot-Noirault
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: David
authors.forename: Aurélien
authors.initials: A
authors.lastname: Vidal
authors.forename: Caroline
authors.initials: C
authors.lastname: Peyrode
authors.forename: Sophie
authors.initials: S
authors.lastname: Besse
authors.forename: Marie-Mélanie
authors.initials: MM
authors.lastname: Dauplat
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Heymann
authors.forename: François
authors.initials: F
authors.lastname: Gouin
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Chezal
authors.forename: Dominique
authors.initials: D
authors.lastname: Heymann
authors.forename: Françoise
authors.initials: F
authors.lastname: Rédini