99mTc-NTP 15-5 assessment of the early therapeutic response of chondrosarcoma to zoledronic acid in the Swarm rat orthotopic model.

Elisabeth Miot-Noirault 1, * Emmanuelle David 2 Aurélien Vidal 1 Caroline Peyrode 1 Sophie Besse 1 Marie-Mélanie Dauplat 3 Marie-Françoise Heymann 2, 4 François Gouin 2, 5 Jean-Michel Chezal 1 Dominique Heymann 2 Françoise Rédini 2
* Auteur correspondant
1 IMTV - Imagerie Moléculaire et Thérapie Vectorisée
2 Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives
3 Service d'anatomo-pathologie
4 Service d'anatomo-pathologie
5 Service d'orthopédie
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. FINDINGS: Rats bearing chondrosarcoma in the orthotopic paratibial location were treated by ZOL (100 mug/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.
keyword : Chondrosarcoma Zoledronic acid 99mTc-NTP 15-5 radiotracer Proteoglycans
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Article dans une revue
EJNMMI Research, BioMed Central, 2013, 3 (1), pp.40. 〈10.1186/2191-219X-3-40〉
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Elisabeth Miot-Noirault, Emmanuelle David, Aurélien Vidal, Caroline Peyrode, Sophie Besse, et al.. 99mTc-NTP 15-5 assessment of the early therapeutic response of chondrosarcoma to zoledronic acid in the Swarm rat orthotopic model.. EJNMMI Research, BioMed Central, 2013, 3 (1), pp.40. 〈10.1186/2191-219X-3-40〉. 〈inserm-00827007〉

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