Bifunctional chelators for radiorhenium: past, present and future outlook

Targeted radionuclide therapy (TRNT) is an ever-expanding field of nuclear medicine that provides a personalised approach to cancer treatment while limiting toxicity to normal tissues. It involves the radiolabelling of a biological targeting vector with an appropriate therapeutic radionuclide, often facilitated by the use of a bifunctional chelator (BFC) to stably link the two entities. The radioisotopes of rhenium, Re-186 (t(1/2) = 90 h, 1.07 MeV beta(-), 137 keV gamma (9%)) and Re-188 (t(1/2) = 16.9 h, 2.12 MeV beta(-), 155 keV gamma (15%)), are particularly attractive for radiotherapy because of their convenient and high-abundance beta(-)-particle emissions as well as their imageable gamma-emissions and chemical similarity to technetium. As a transition metal element with multiple oxidation states and coordination numbers accessible for complexation, there is great opportunity available when it comes to developing novel BFCs for rhenium. The purpose of this review is to provide a recap on some of the past successes and failings, as well as show some more current efforts in the design of BFCs for Re-186/188. Future use of these radionuclides for radiotherapy depends on their cost-effective availability and this will also be discussed. Finally, bioconjugation strategies for radiolabelling biomolecules with Re-186/188 will be touched upon.