Chemical exchange saturation transfer (CEST) is a relatively new contrast mechanism for MRI. CEST MRI exploits a specific MR frequency (chemical shift) of a molecule while generating an image with good spatial resolution using standard MRI techniques, combining the specificity of MRS with the spatial resolution of MRI. Many CEST MRI acquisition methods have been developed to improve analyses of tumor metabolism. GluCEST, CrCEST, and LATEST can map glutamate, creatine, and lactate, which are important metabolites involved in tumor metabolism. GlucoCEST MRI tracks the pharmacokinetics of glucose transport and cell internalization within tumors. CatalyCEST MRI detects enzyme catalysis that changes a substrate CEST agent. AcidoCEST MRI measures extracellular pH of the tumor microenvironment by exploiting a ratio of two pH-dependent CEST signals. This review describes each technique, the technical issues involved with CEST MRI and each specific technique, and the merits and challenges associated with applying each CEST MRI technique to study tumor metabolism.

Purpose We sought to determine if the synergy between evaluations of glucose uptake in tumors and extracellular tumor acidosis measured with simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) can improve longitudinal evaluations of the response to metformin treatment. Procedures A standard 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET protocol that evaluates glucose uptake in tumors, and a standard acidoCEST MRI protocol that measures extracellular pH (pHe) in tumors, were simultaneously performed to assess eight vehicle-treated (control) mice and eight metformin-treated mice 1 day before treatment, 1 day after initiating daily treatment with metformin, and 7 days after initiating treatment. Longitudinal changes in SUVmax and extracellular pH (pHe) were evaluated for each treatment group, and differences in SUVmax and pHe between metformin-treated and control groups were also evaluated. Results MRI acquisition protocols had little effect on the PET count rate, and the PET instrumentation had little effect on image contrast during acidoCEST MRI, verifying that [18F]FDG PET and acidoCEST MRI can be performed simultaneously. The average SUVmax of the tumor model had a significant decrease after 7 days of treatment with metformin, as expected. The average tumor pHe decreased after 7 days of metformin treatment, which reflected the inhibition of the consumption of cytosolic lactic acid caused by metformin. However, the average SUVmax of the tumor model was not significantly different between the metformin-treated and control groups after 7 days of treatment, and average pHe was also not significantly different between these groups. For comparison, the combination of average SUVmax and pHe measurements significantly differed between the treatment group and control group on Day 7. Conclusions [18F]FDG PET and acidoCEST MRI studies can be performed simultaneously. The synergistic combination of assessing glucose uptake and tumor acidosis can improve differentiation of a drug-treated group from a control group during drug treatment of a tumor model.

Purpose We sought to investigate the potential of D-maltose, D-sorbitol, and D-mannitol as T2 exchange magnetic resonance imaging (MRI) contrast agents. We also sought to compare the in vivo pharmacokinetics of D-maltose with D-glucose with dynamic contrast enhancement (DCE) MRI. Methods T1 and T2 relaxation time constants of the saccharides were measured using eight pH values and nine concentrations. The effect of echo spacing in a multiecho acquisition sequence used for the T2 measurement was evaluated for all samples. Finally, performances of D-maltose and D-glucose during T2-weighted DCE-MRI were compared in vivo. Results Estimated T2 relaxivities (r2) of D-glucose and D-maltose were highly and nonlinearly dependent on pH and echo spacing, reaching their maximum at pH=7.0 (~0.08mM−1 s−1). The r2 values of D-sorbitol and D-mannitol were estimated to be ~0.02mM−1 s−1 and were invariant to pH and echo spacing for pH ≤7.0. The change in T2 in tumor and muscle tissues remained constant after administration of D-maltose, whereas the change in T2 decreased in tumor and muscle after administration of D-glucose. Therefore, D-maltose has a longer time window for T2-weighted DCE-MRI in tumors. Conclusion We have demonstrated that D-maltose can be used as a T2 exchange MRI contrast agent. The larger, sustained T2-weighted contrast from D-maltose relative to D-glucose has practical advantages for tumor diagnoses during T2-weighted DCE-MRI.