Medical Advances in F19 MRI: Imaging Drugs in Living Organisms

[gravenewworld]

What kind of advances have been made in this field (since I don't stay on top of it)? If I wanted to image, say, where my fluorinated drug is going within a rat, is it possible? NMR is inherently not a sensitive modality. Hydrogen is vastly more abundant in a living organism than fluorine (typical MRI vs F19 MRI), so given the fact that most therapeutic doses of drugs occur probably in the millimolar to nanomolar range, is it even possible to produce a good image with F19 MRI? Is it practically impossible to produce a decent S/N ratio? What if I incorporated more fluorines into my compound?

 

[Mike H]

I recall people were fiddling around with hyperpolarization schemes in relation to ¹⁹F MRS/MRI at an Experimental NMR Conference a few years back, but they were able to get the model system/proof of concept looking fairly convincing, so you might want to poke around to see if they've made the jump to the clinic (or at least the diagnostic radiology research labs).

Otherwise, more fluorines = more signal. Jeff Bulte at Johns Hopkins has been using extensively fluorinated compounds as contrast agents/tracers that I can also muster up from memory within the last few years. Also, in general, fluorine has some particularly interesting advantages - it's about 80% to 85% as sensitive as ¹H, the only stable isotope is ¹⁹F (in contrast to hydrogen and deuterium), and it's a spin-1/2 nucleus.

 

[gravenewworld]

Thanks for the response. My PI just sent me this paper in which they have a moiety containing a CF3 group complexed with a lanthanide metal

http://onlinelibrary.wiley.com/doi/10.1002/mrm.22881/abstract

Sensitivity for 19F increases by 10,000 fold. Would this work for boron instead of a lanthanide? For example a compound containing a BF2 group? My quantum chemistry is quite rusty (took it almost 10 years ago), so I'm not sure if using boron would also work to decrease relaxation times too.

 

[Mike H]

The most common boron nuclei are quadrupolar, so my initial suspicion is that they would indeed facilitate faster relaxation times. Relative to a comparable lanthanide complex...not sure off the top of my head. I would suspect probably not, although it would depend on which one. I'm mostly thinking that you may find naturally occurring lanthanides to be a mix of isotopes, some of which are themselves quadrupolar (for example - "natural abundance" gadolinium is actually composed of 5 or 6 isotopes, some of which are spin-3/2 nuclei). I think there are some lanthanides which are mostly just spin-1/2 nuclei (thulium, I think, as it's used in the shift reagent TmDOTP), but my rare-earth chemistry is a bit dusty.