Visualization of Cervical Cancers with MRI-Based Metabolic Imaging
Abstract
Purpose
18F-fluorodeoxygluose positron emission tomography (18F-FDG-PET) is clinically useful in cervical cancer care and has been shown to reduce interobserver variation of the residual gross tumour volume in brachytherapy. Chemical exchange saturation transfer MRI with glucose-based contrast agents has been suggested as a non-radioactive, non-toxic alternative to 18F-FDG-PET. While many CEST studies have utilized D-glucose (D-Glc), it is not directly analogous to FDG as it is fully metabolized rather than accumulating intracellularly. D-glucosamine (D-GlcN), an amino monosaccharide, is phosphorylated like FDG then slowly metabolized, exhibiting favourable uptake kinetics and safety. D-GlcN CEST successfully visualized human breast cancer, but has yet to be applied to cervical cancer. Following a pilot small animal study with D-Glc, this work aims to assess D-GlcN CEST as an alternative to 18F-FDG-PET for cervical cancer imaging, beginning with phantom characterization.
Methods
NMR tubes containing 0-20mM D-GlcN in PBS (pH 6.6) were imaged at 7T (Bruker Biospec MRI; 40 mm inner diameter quadrature RF coil) using a CEST-RARE sequence (TR =10s, 64 x 64 matrix, RARE factor=16, NEX=1, 5s presaturation block pulse at 2µT, 29 frequency offsets –3.5 and 0.35 ppm, 0.25ppm increments). B0 inhomogeneity was corrected through spline interpolation and saturation transfer was calculated through asymmetry analysis (Moritz Zaiss, Matlab2023b).
Results
The strongest MR signal modulation was observed at 1 ppm, consistent with literature. This signal modulation ranged from 1 to 16% across D-GlcN concentrations from 0 to 20 mM. Saturation transfer increased linearly with D-GlcN concentration at a rate of 0.007/mM.
Conclusion
D-GlcN is a CEST contrast agent with potential utility in cervical cancer visualization. The measured CEST effect of D-GlcN at relevant concentrations and pH suggests the feasibility of this methodology for a small animal study, in which mice carrying ME180 human cervical cancer orthotopic tumours are imaged before and after injection of D-GlcN.