A new chemical reaction enables synthesis of unique cancer imaging agents 

The motivation – The early and accurate detection of cancer is critical for the clinical management of cancer. One promising technique for cancer detection is positron emission tomography (PET), where a patient is administered a low dose of a drug containing a radioisotope or 'radiotracer' that collects in cancerous cells and reports their precise location to an oncologist who then decides on a treatment regime. Key to the success of this technique is a selective interaction of the drug and cancerous cells such that the drug accumulates in the cells. Among the many possible radioisotopes that can be used, fluorine-18 (18F) is ideal due to its favourable chemical properties and an existing worldwide network for its production. Unfortunately, advances in this area have been prevented due to the technically challenging problems faced by chemists tackling the synthesis of 18F-containing radiotracers.

The discovery – Recently, Simon Fraser University (SFU) researchers discovered a unique and mild chemical reaction that enables the direct incorporation of 18F into various drug molecules. Importantly, for the first time, they also showed that aliphatic amino acids (i.e., amino acids that contain nonpolar or hydrophobic side chains) can be directly fluorinated and thus converted into radiotracers. Exploiting their unique capabilities, in collaboration with researchers at the Canadian subatomic physics laboratory TRIUMF, the British Columbia Cancer Agency and F. Hoffman-La Roche, the Britton Group rapidly synthesized a panel of 18F-labelled amino acids that would otherwise be extremely challenging to produce and then examined their utility as PET imaging agents for cancer. From this study, they discovered that the previously unknown 18F-labelled amino acid 5-[18F]fluorohomoleucine (5-[18F]FHL) accumulates in cancer cells and is an excellent tumor imaging agent in animal models.

Its significance – Clinicians can now easily and rapidly access radiotracers that may improve the methods of detecting cancer and monitoring disease progression, which will benefit the lives of many people.

Read the paper – “18F-Fluorination of unactivated C–H bonds in branched aliphatic amino acids: Direct synthesis of oncological positron emission tomography imaging agents” by Matthew B. Nodwell, Hua Yang, Milena Čolović, Zheliang Yuan, Helen Erkens, Rainer E. Martin, François Bénard, Paul Schaffer, and Robert Britton. J. Am. Chem. Soc. 139(10):3595–3598 (2017). DOI: 10.1021/jacs.6b11533

Website article compiled by Jacqueline Watson with Theresa Kitos