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Simultaneous proteoglycans and hypoxia mapping of chondrosarcoma environment by frequency selective CEST MRI
Author(s) -
Autissier Roxane,
Mazuel Leslie,
Maubert Elise,
Bonny JeanMarie,
Auzeloux Philippe,
Schmitt Sébastien,
Traoré Amidou,
Peyrode Caroline,
MiotNoirault Elisabeth,
Pagés Guilhem
Publication year - 2021
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.28781
Subject(s) - ex vivo , chondrosarcoma , in vivo , chemistry , hypoxia (environmental) , proteoglycan , pathology , magnetic resonance imaging , preclinical imaging , cartilage , nuclear medicine , medicine , in vitro , anatomy , radiology , biology , oxygen , biochemistry , microbiology and biotechnology , organic chemistry
Purpose To evaluate the relevance of CEST frequency selectivity in simultaneous in vivo imaging of both of chondrosarcoma’s phenotypic features, that are, its high proteoglycan concentration and its hypoxic core. Methods Swarm rat chondrosarcomas were implanted subcutaneously in NMRI nude mice. When tumors were measurable (12‐16 days postoperative), mice were submitted to GAG, guanidyl, and APT CEST imaging. Proteoglycans and hypoxia were assessed in parallel by nuclear imaging exploiting 99m Tc‐NTP 15‐5 and 18 F‐FMISO, respectively. Data were completed by ex vivo analysis of proteoglycans (histology and biochemical assay) and hypoxia (immunofluorescence). Results Quantitative analysis of GAG CEST evidenced a significantly higher signal for tumor tissues than for muscles. These results were in agreement with nuclear imaging and ex vivo data. For imaging tumoral pH in vivo, the CEST ratio of APT/guanidyl was studied. This highlighted an important heterogeneity inside the tumor. The hypoxic status was confirmed by 18 F‐FMISO PET imaging and ex vivo immunofluorescence. Conclusion CEST MRI simultaneously imaged both chondrosarcoma properties during a single experimental run and without the injection of any contrast agent. Both MR and nuclear imaging as well as ex vivo data were in agreement and showed that this chondrosarcoma animal model was rich in proteoglycans. However, even if tumors were lightly hypoxic at the stage studied, acidic areas were highlighted and mapped inside the tumor.