Methods to increase the metabolic stability of ¹⁸F-radiotracers

The majority of pharmaceuticals and other organic compounds including radiotracers that are considered foreign to the body undergo metabolic changes in vivo. Most of these compounds are metabolic degraded by a system of enzymes of low substrate specificity requirement which is present mainly in the liver but drug metabolism may also take place in the kidneys or other organs. Thus, radiotracers and all other pharmaceuticals are faced with enormous challenges to maintain their stability in vivo implicating a high requirement on their structure. Often in practice, such biologically active molecules with manifested properties are found in vitro but these results could not be confirmed in vivo due to an increased metabolism within minutes. Many pharmacologically and biologically interesting compounds fail for further application due to their lack of stability.
One of the most important issues of radiotracers development based on fluorine-18 is the stability in vitro and in vivo. Sometimes, the metabolism of ¹⁸F-radiotracers goes along with the cleavage of the F-C bond and with the rejection of [¹⁸F]fluoride mostly combined with high background and accumulation in the skeleton. This review deals with the impact of radiodefluorination and with approaches to stabilize the F-C bond to avoid the cleavage between fluorine and carbon.