Long arms may be useful for reaching the biscuit tin but scientists in the US have shown that shorter arms are better for radiopharmaceuticals.

A team of chemists led by Edward Wong and Gary Weisman at the University of New Hampshire, Durham, and Carolyn Anderson at the Washington University School of Medicine, Missouri, has been investigating molecules that combine with copper to make radiopharmaceuticals. Radioisotopes such as ⁶⁴Cu can be used for both the diagnosis and targeted therapy of cancer, but a carrier is needed to get the copper to where it is needed. 

Wong's team had previously found a molecule that chelates (or binds) copper(II) extremely strongly. The molecule consists of a 14-membered ring, known as a macrocycle, that has carboxylic acid groups dangling on pendant arms. Now the scientists have investigated how varying the lengths of the arms changes the way the molecule binds to copper.

The results showed that having longer arms made it easier to reduce the copper-complex to copper(I), which results in the metal breaking free from the ligand, in a process called demetallation. The longer armed molecules also proved to be less stable during in vivo testing.

The researchers plan to work on improving the binding kinetics of the complexes and reducing the harsh conditions currently needed to make the radiopharmaceuticals. They also intend to expand the work to other metals. 'Although radio-copper chelation has been a major goal, we anticipate that other radiometals such as gallium and indium will also form very robust complexes with this family of chelators and expand their application potential,' said Wong.

Laura Howes