This is a linkpost for https://www.bhauth.com/blog/biology/mri%20tracers.html
Is there a signal-to-noise problem if you don't do hyperpolarization, and just give someone an isotopically enriched molecule?
17O seems like a good try for that, because of low natural abundance and decent NMR properties.
Is there a signal-to-noise problem if you don't do hyperpolarization, and just give someone an isotopically enriched molecule
Yes.
17O seems like a good try for that
MRI with oxygen-17 has been done. Here's a study from 1990. And here's a more recent paper which mentions some reasons it hasn't been widely used, including:
MRI scans and PET scans 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 and fMRI.
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:
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 as a MRI tracer. You can make tracers using that by:
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 notes:
People then looked at stable nitroxides, such as TEMPO. There's been a recent resurgence of interest in those. As this paper notes:
So, here's a paper testing MRI with nitroxide tracers as a way to observe redox activity in cells. It concludes:
Overall, this approach doesn't seem as useful as hyperpolarized carbon-13, but it's interesting.