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Simon Muller
Simon Muller

Radioactivity really hasn’t the healthiest reputation: the  disasters of Fukushima and Tschernobyl, the devastation wrought  by atomic bombs, or the nuclear waste issue we face around the world just to name the front-runners. And although a number of scientists argue that technological  advances and efficient recycling have made nuclear plants and similar technologies safer, radioactivity scares us.

It scares us especially because it is a danger we cannot spot visually but which can nevertheless have very real and long-lasting effects. At the same time, radioactive markers can actually make us see things we could not see otherwise – through imaging.

Nuclear power is highly controversial, but sometimes heavy atom based techniques are very desirable! [i]

The idea of imaging tackles two of the most fundamental issues in modern medicine:

how can we detect a disease and how can we find out if our treatment is successful?

You will have surely encountered some medical imaging techniques in your life such as diagnostic ultrasonography (famous for being used during pregnancy), X-ray radiography or magnetic resonance imaging (when I did that 10 years ago, I had to be under these gigantic magnets and had to lie still for 45 minutes while having the impression of being on a construction site).  Another very powerful imaging technique is positron emission tomography (PET) and it gives us insights hardly any other method can give us.

 

Picture of a full body PET scan[ii]

So how does PET work?

A radioactively labelled compound is injected into your veins. But no worries, it is not plutonium that people pump into you, but an organic molecule with radioactively labelled fluorine. [18] Fluorine has a half-life of 110 minutes, so you don’t have to worry about long radiation effects or anything comparable. However, PET is not completely without risks, so it is usually only applied in very severe diseases such as cancer or dementia. The radioactive fluorine leads to γ-radiation which is then detected by the scanner and gives information on  tissues and organs[iii].

 

Let’s explain this in a bit more detail based on the most common molecule for PET imaging: fluorodeoxyglucose.

 

Glucose is a molecule you surely know. It’s the most common sugar of all, the one you put in your coffee, into your cookies and cakes. In the case of fluorodeoxyglucose, one of the functional groups (a hydroxyl group) is exchanged for radioactive fluorine. Some of our cells need more glucose than others, just as some of us need more sugar than others (I’m definitely part of the high glucose intake cells…especially when we are talking chocolate!).

These cells are in particular kidney, brain and cancer cells. Therefore, fluorodeoxyglucose can give us insights into these kinds of cells, as it is absorbed by cells  in just the same manner as normal Glucose (however, it is not further processed!).

 

Through PET scanning fluorodeoxyglucose can then show us cancer distributions, how the cancer treatment is influencing cancer growth or how it can be used to detect Alzheimer’s disease.

video: “Understanding Radiology: What is a PET Scan?” by Baylor Health Care System

 

A short video explaining in simple words how PET works

Positron emission tomography is not limited to fluorodeoxyglucose, one can easily imagine how different kinds of compounds could give us very diverse information about all kinds of diseases. The major limitation of PET lies in a very fascinating problem which has received considerable attention within the scientific community.

 

It is: How do you get the radioactive fluorine into our molecules?

Just think about it! Radioactive 18F has a half-life of 110 minutes, but a classical organic synthesis of complex compounds can take weeks to months! There will be no radioactivity anymore by then, and the compound will have lost all of our interest. Unfortunately, we cannot just synthesize our entire molecule with normal fluorine first and then use a cyclotron to produce 18F, it would blast our molecule into pieces!

So, we need to find ways to introduce radioactively labelled fluorine as late into our molecule as possible, in a very quick and reliable reaction (to make things even more challenging, one has to work on very tiny quantities at  the nanogram scale, so that there is no risk from too much radioactive material).

 

Chemists all around the world are working on strategies to solve this problem and they have found some really beautiful solutions.

 

What I personally really like about the synthesis of 18F-compounds is that chemists try to find a solution for a problem of a completely different field. It is really an example of the kind of interdisciplinary research that the media talks about so much. It also shows how creative people can be when facing an entirely unexpected problem, because a chemist would never have thought about introducing fluorine at a late-stage within a synthesis without PET scanning.

In this special case, radioactivity has not only brought us a powerful imaging technique in medicine but also some very fascinating and new chemistry!

 


[i] http://en.wikipedia.org/wiki/Smiling_Sun

[ii] http://en.wikipedia.org/wiki/File:PET-MIPS-anim.gif

[iii] The radioactive fluorine emits a positron which subsequently releases γ-radiation after breakdown.

[iv] http://en.wikipedia.org/wiki/File:Glucose_metabolism.svg

[v] http://en.wikipedia.org/wiki/File:Fludeoxyglucose_18-F_skeletal.svg