Simultaneous proteoglycans and hypoxia mapping of chondrosarcoma environment by frequency selective CEST MRI

Area of Science:

• Biomedical Imaging
• Oncology
• Biochemistry

Background:

• Chondrosarcoma exhibits distinct phenotypic features, including high proteoglycan concentration and hypoxic cores.
• Accurate in vivo assessment of these features is crucial for understanding tumor biology and guiding treatment.
• Current imaging modalities may have limitations in simultaneously evaluating these diverse characteristics.

Purpose of the Study:

• To evaluate the relevance of Chemical Exchange Saturation Transfer (CEST) frequency selectivity for simultaneous in vivo imaging of chondrosarcoma's proteoglycan concentration and hypoxic core.
• To assess the utility of CEST MRI as a contrast-agent-free imaging technique for these phenotypic features.

Main Methods:

• Swarm rat chondrosarcomas were implanted in NMRI nude mice.
• Mice underwent GAG, guanidyl, and APT CEST imaging.
• Proteoglycans and hypoxia were assessed in parallel using nuclear imaging (^99m Tc-NTP 15-5 and ¹⁸ F-FMISO) and ex vivo analyses (histology, biochemical assays, immunofluorescence).

Main Results:

• Quantitative analysis of GAG CEST showed significantly higher signal in tumor tissues compared to muscles, consistent with nuclear imaging and ex vivo data.
• CEST ratio of APT/guanidyl highlighted significant heterogeneity in tumoral pH.
• ¹⁸ F-FMISO PET imaging and ex vivo immunofluorescence confirmed the hypoxic status of the tumors.

Conclusions:

• CEST MRI enables simultaneous in vivo imaging of chondrosarcoma's proteoglycan content and hypoxic regions within a single experimental session, without contrast agents.
• The study confirmed the chondrosarcoma model's high proteoglycan content and identified acidic, hypoxic areas within the tumor, demonstrating CEST MRI's potential for comprehensive tumor characterization.