Molecular imaging of tumors by chemical exchange saturation transfer MRI of glucose analogs

Early detection of the cancerous process would benefit greatly from imaging at the cellular and molecular level. Increased glucose demand has been recognized as one of the hallmarks of cancerous cells (the "Warburg effect"), hence glucose and its analogs are commonly used for cancer imaging. One example is FDG-PET technique, that led to the use of chemical exchange saturation transfer (CEST) MRI of glucose ("glucoCEST") for tumor imaging. This technique combines high-resolution MRI obtained by conventional imaging with simultaneous molecular information obtained from the exploitation of agents with exchangeable protons from amine, amide or hydroxyl residues with the water signal. In the case of glucoCEST, these agents are based on glucose or its analogs. Recently, preclinical glucoCEST studies demonstrated the ability to increase the sensitivity of MRI to the level of metabolic activity, enabling identification of tumor staging, biologic potential, treatment planning, therapy response and local recurrence, in addition to guiding target biopsy for clinically suspected cancer. However, natural glucose limits this method because of its rapid conversion to lactic acid, leading to reduced CEST effect and short signal duration. For that reason, a variety of glucose analogs have been tested as alternatives to the original glucoCEST. This review discusses the merits of these analogs, including new data on glucose analogs heretofore not reported in the literature. This summarized preclinical data may help strengthen the translation of CEST MRI of glucose analogs into the clinic, improving cancer imaging to enable early intervention without the need for invasive techniques. The data should also broaden our knowledge of fundamental biological processes.