The two glucose analogs 2-deoxy-D-glucose (2-DG) and 2-fluoro-2-deoxy-D-glucose (FDG) are preferentially taken up by cancer cells, undergo phosphorylation and accumulate in the cells. Owing to their exchangeable protons on their hydroxyl residues they exhibit significant chemical exchange saturation transfer (CEST) effect in MRI. Here we report CEST-MRI on mice bearing orthotopic mammary tumors injected with 2-DG or FDG. The tumor exhibited an enhanced CEST effect of up to 30% that persisted for over one hour. Thus 2-DG/FDG CEST MRI can replace PET/CT or PET/MRI for cancer research in laboratory animals, but also has the potential to be used in the clinic for the detection of tumors and metastases, distinguishing between malignant and benign tumors and monitoring tumor response to therapy as well as tumors metabolism noninvasively by using MRI, without the need for radio-labeled isotopes.

Aims To determine individual glucose hydroxyl exchange rates at physiological conditions and use this information for numerical optimization of glucoCEST/CESL preparation. To give guidelines for in vivo glucoCEST/CESL measurement parameters at clinical and ultra‐high field strengths. Methods Five glucose solution samples at different pH values were measured at 14.1 T at various B1 power levels. Multi‐B1‐Z‐spectra Bloch‐McConnell fits at physiological pH were further improved by the fitting of Z‐spectra of five pH values simultaneously. The obtained exchange rates were used in a six‐pool Bloch‐McConnell simulation including a tissue‐like water pool and semi‐solid MT pool with different CEST and CESL presaturation pulse trains. In vivo glucose injection experiments were performed in a tumor mouse model at 7 T. Results and discussion Glucose Z‐spectra could be fitted with four exchanging pools at 0.66, 1.28, 2.08 and 2.88 ppm. Corresponding hydroxyl exchange rates could be determined at pH = 7.2, T = 37°C and 1X PBS. Simulation of saturation transfer for this glucose system in a gray matter‐like and a tumor‐like system revealed optimal pulses at different field strengths of 9.4, 7 and 3 T. Different existing sequences and approaches are simulated and discussed. The optima found could be experimentally verified in an animal model at 7 T. Conclusion For the determined fast exchange regime, presaturation pulses in the spin‐lock regime (long recover time, short yet strong saturation) were found to be optimal. This study gives an estimation for optimization of the glucoCEST signal in vivo on the basis of glucose exchange rate at physiological conditions.

Due to the large CEST effect of 3OMG and its low toxicity 3OMG-CEST may serve for the detection of tumors and metastases in the clinic.

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.

The efficacy of glucosamine (GlcN) and N-acetyl glucosamine (GlcNAc) as agents for chemical exchange saturation transfer (CEST) magnetic resonance molecular imaging of tumors is demonstrated. Both agents reflect the metabolic activity and malignancy of the tumors. The method was tested in two types of tumors implanted orthotopically in mice: 4T1 (mouse mammary cancer cells) and MCF7 (human mammary cancer cells). 4T1 is a more aggressive type of tumor than MCF7 and exhibited a larger CEST effect. Two methods of administration of the agents, intravenous (IV) and oral (PO), gave similar results. The CEST MRI observation of lung metastasis was confirmed by histology. The potential of the clinical application of CEST MRI with these agents for cancer diagnosis is strengthened by their lack of toxicity as can be indicated from their wide use as food supplements.