1. CHEMISTRY 1000 Topics of Interest #3: Acid, Baking Soda and Cancer

2. Acidity and Illness Tissues containing cancerous cells (or fighting off an infection) tend to be more acidic than healthy tissues. If we could measure tissue pH non-invasively, we could potentially use that to detect cancer. We could also use it to monitor whether a tumour is growing or shrinking in response to treatment. Magnetic Resonance Imaging (MRI) allows us to examine the chemical environment of all atoms of a particular isotope. The original form of this technology is widely used in chemistry labs where it goes by the name Nuclear Magnetic Resonance (NMR) because it is looking at the chemical environment around a nucleus. It is a major topic of Organic Chemistry 2 (CHEM 2600). F.A. Gallagher et al Nature (2008) 453, 940-943

3. Detecting Acidity in Tissue At first glance, you might think that the way to look for acidity in tissue would be to look at all of the 1 H atoms and see how many exist as H +. This might work in theory but, in practice, signals from all of the other 1 H atoms in the cell would probably obscure the signal. We need to use an isotope that’s not as common in the body so that we can just look at it. MRI doesn’t work well on 2 H, and 3 H is radioactive, so we want to look at elements other than hydrogen. We need something safe to put in our bodies that will contain an uncommon (and non-radioactive!) isotope and that will react with acid. F.A. Gallagher et al Nature (2008) 453, 940-943

4. Detecting Acidity in Tissue The pH of our blood is maintained by buffers – one of which is a carbonate buffer (i.e. a mixture of CO 2, HCO 3 - and CO 3 2- where the ratio of the three species determines/is determined by pH). Looking at 12 C would be as difficult as looking at 1 H but, if we added HCO 3 - containing 13 C instead of 12 C, we could then look at what happened to the 13 C! When HCO 3 - reacts with acid, CO 2 is produced, so when H 13 CO 3 - reacts with acid, 13 CO 2 is produced: so F.A. Gallagher et al Nature (2008) 453, 940-943

5. Detecting Acidity in Tissue We can see that the two 13 C atoms are in different chemical environments. NMR can tell that too (see right) and can tell what fraction of 13 C atoms are in H 13 CO 3 - and what fraction are in 13 CO 2. F.A. Gallagher et al Nature (2008) 453, 940-943

6. Detecting Acidity in Tissue The images below show a section of mouse tissue containing a tumour. In the image on the left, the tumour is outlined in red. In the image on the right, we can see the tumour using this imaging technique! F.A. Gallagher et al Nature (2008) 453, 940-943