# MRI tracers

MRI scans and [PET scans](https://en.wikipedia.org/wiki/Positron_emission_tomography) are different methods for medical imaging, and they observe different things:

- MRI scans can see which nuclei are present in regions. Sometimes bond types of particular elements can be distinguished, eg in [1H NMR](https://en.wikipedia.org/wiki/Proton_nuclear_magnetic_resonance) and [fMRI](https://en.wikipedia.org/wiki/Functional_magnetic_resonance_imaging).

- PET scans add a short-lived radioactive tracer (usually organic molecules with radioactive fluorine added to them) and observe where decays happen. This can track things like movement of glucose in the body. The half-life of fluorine-18 is ~110 minutes. PET scans are often combined with CT or MRI to correlate tracers with locations of organs.

Of course, MRI scans are generally preferably because they don't expose patients or staff to radiation, and don't require short-lived radioactive compounds. That being the case, who among us hasn't asked:

> Could we use tracer compounds for MRI scans that let MRI do what PET is used for?

Historically, such tracers for MRI weren't available, but there are now some interesting options. (Yes, metallic contrast agents (eg gadolinium) have been used with MRI, but that doesn't do what we need here.)


## hyperpolarized carbon-13

1.1% of carbon is 13C, which is stable and basically harmless. Hyperpolarized 13C has a fairly strong MRI signal and [can be used](https://pmc.ncbi.nlm.nih.gov/articles/PMC10546364/) as a MRI tracer. You can make tracers using that by:

1. Getting some 13C.
2. Making some relevant molecule, like pyruvate or acetate. Unlike PET tracers, this doesn't need to be done right before they're used.
3. Polarizing the 13C. Basically, you get it very cold, and put it in a strong magnet until it goes all wibbly.

While the compounds are stable, the polarization decays quickly. Pyruvate spin lattice relaxation time (T1) is ~50-70 seconds ex vivo and ~20-30 seconds in vivo. Sufficient signal for detection is present for ~5x the T1. In that time, the tracer needs to be warmed up, injected, and detected by a scan.

So, you need a strong magnet, and special equipment for quickly processing the tracer during a MRI scan. Few hospitals are currently set up to do this, but technologically it's easier than the MRI scan itself.



## nitroxide radicals

An obvious idea for MRI tracers is to use a metal contrast agent (eg gadolinium) in some organic complex attached to an antibody. That didn't work very well. [This 1985 paper](https://journals.lww.com/investigativeradiology/abstract/1985/10000/magnetic_resonance_imaging_using_gadolinium.8.aspx) notes:

> For monoclonal antibodies to function as selective MR contrast agents, substantial advances in technology must occur.

People then looked at stable nitroxides, such as [TEMPO](https://en.wikipedia.org/wiki/TEMPO). There's been a recent resurgence of interest in those. As [this paper](https://journals.sagepub.com/doi/full/10.1038/jcbfm.2008.5) notes:

> The rapid bioreduction from paramagnetic nitroxides to the corresponding diamagnetic hydroxylamines has compromised their utility as contrast agents (Keana and Pou, 1985). The combination of relatively low relaxivity and short life spans precluded the use of nitroxides as MRI contrast agents. However, with improved sensitivity of MRI and shift to higher magnetic fields, recent work has begun to investigate whether the reduction of nitroxides might be useful in obtaining information pertaining to the redox status of tissue.

So, [here's a paper](https://www.liebertpub.com/doi/full/10.1089/ars.2021.0110) testing MRI with nitroxide tracers as a way to observe redox activity in cells. It concludes:

> Redox imaging is a useful tool to detect an abnormal tissue redox status such as disordered oxidative stress or tumor hypoxia. Data from nitroxyl-enhanced MRI/EPRI in vivo must be considered and interpreted carefully because the kinetics of the signal in the target tissue or organ depend on a number of factors.

Overall, this approach doesn't seem as useful as hyperpolarized carbon-13, but it's interesting.