As compared to other molecular imaging techniques (esp. those based on SPECT or PET imaging) MRI in general has a notorious low sensitivity. One way to increase sensitivity is increasing the payload of MRI contrast agents (paramagnetic and/or superparamagnetic agents) or tracers (perfluorocarbons) in the form of nanoparticles. This has worked well for in vivo cell tracking, using in situ labeling of macrophages or ex vivo labeling of therapeutic immune cells and stem cells. However, the number of clinical MRI cell tracking studies have been few (1), having its roots in the paucity of available GMP-grade labeling agents, their cost of production and testing, and the need for cumbersome IND approval for their off-label use (unlike the use of radionuclides, where often the microdosing tracer principle applies). Chemical exchange saturation transfer (CEST) MRI tracking of unlabeled cells would avoid these hurdles, but has so far only been applied to mesenchymal stem cells (2).
For detecting specific molecular targets, widely done clinically in nuclear medicine with an emphasis on cancer, MRI has been overall disappointing. This is mainly due to the sheer size of the nanoscale agents, leading to unfavorable tissue penetration and pharmacokinetic properties, with rapid clearance by the reticulo-endothelial system (RES). One strategy to enhance tumor targeting and retention of MRI contrast agents is to inject small molecules that undergo a tumor-specific enzymatic reaction resulting in the formation of nanoparticles which prevents the agent from being pumped out of the cell, as exemplified for the diaCEST contrast olsalazine (3). Using this strategy, RES uptake is negligible with excretion of non-bound agent through the urinary tract. In this educational lecture, I will aim to discuss some of the latest directions in the design and use of nanoscale MR imaging agents, including the use of multi-spectral agents, pH imaging agents, and functional agents sensing the tumor microenvironment. I will also discuss how certain MRI studies using superparamagnetic iron oxides and perfluorocarbons are now being duplicated using magnetic particle imaging (MPI), and review the advantages and disadvantages of the two modalities from a clinical perspective.

Acknowledgements

No acknowledgement found.