Amide proton transfer MR imaging of prostate cancer: a preliminary study.

Magnetic Resonance (MR) imaging can play an important role in the management of prostate cancer. MR imaging techniques, such as dynamic contrast-enhanced MR imaging based on microvasculature and microenvironment (1,2), diffusion-weighted MR imaging based on cellular membrane integrity (3,4), and MR spectroscopic imaging based on metabolites which are cellular/molecular imaging biomarkers (5,6) have shown to be valuable addition to anatomical imaging in prostate cancer detection and tumor staging. Multi-parametric MR imaging enables better prostate cancer detection by incorporating these techniques (7–10). Imaging-based prostate cancer management may be improved by using a new MR imaging method based on endogenous mobile protein level detection, as investigated in this study. Chemical exchange saturation transfer (CEST) MR imaging has recently emerged as a new molecular imaging technique in which the contrast is determined by a change in water intensity due to chemical exchange with saturated solute protons (11). The CEST-MR imaging technique was first applied to biological tissues by Guivel-Scharen and colleagues (12) who reported that the chemical exchange between la-bile protons of low-concentration solute and water protons provided a sensitivity enhancement scheme that could be used as a new MR imaging contrast mechanism. This imaging technique has been applied to the measurement of pH effect in focal ischemia (13), glycosaminoglycan concentration in knee osteo-arthritis (14), artificial genetically engineered reporter (15), and liver glycogen distribution (16). The CEST approach, using endogenous amide protons (resonance frequency offset at 3.5 ± 0.5 ppm downfield of the water signal) in tissue, was termed amide proton transfer (APT) MR imaging (13). Before the APT-MR imaging method was invented, these mobile proteins were detected using MR spectroscopy with limited spatial resolution (17). APT-MR imaging showed large enhancement in sensitivity (11), thus allowing the detection of micromolar concentrations of mobile proteins in imaging with any existing clinical MR imaging scanners (18). In this study, APT-MR imaging was used for the localization and characterization of prostate cancer. The applicability of APT-MR imaging on prostate cancer detection is based on the fact that high-grade prostate cancer typically shows a higher tumor cell proliferation rate and cellular density, which leads to overall elevated mobile protein levels (19). For example, one of the over-expressed proteins in prostate cancer is an androgen-regulated six trans-membrane protein, which is found to be a highly mobile protein in the cytosol of live cells (20). Another over-expressed protein in human metastatic prostate cancer cells is Caveolin-1 which mediates molecular transport, cell adhesion, and signal transduction activities (21). APT-MR imaging that is in principle sensitive to the concentration of these endogenous mobile proteins may considerably improve our ability to better localize prostate cancer and predict tumor volume and stage. Specifically, the high tumor cell proliferation rate was found in high-grade cancer, but low-grade prostate cancers (Gleason score components and lower) can be slow-growing (22). APT-MR imaging may be a good discriminator between low-grade and high-grade cancers and detect the difference in cancer aggressiveness in prostate cancer management.