New method for producing PET radiotracers

Researchers at the Australian Nuclear Science and Technology Organisation (ANSTO) have led the development of a new method for producing PET radiotracers.

Published in Chemistry – A European Journal, the discovery utilises the transition metal rhenium to promote fluorine-18 radiolabelling under aqueous, low-temperature conditions. This circumvents the need for dry conditions and purification steps, which saves time and offers PET radiotracers in very high yields.

Fluorine-18, the most commonly used radioisotope in PET imaging, must be attached to vectors in order to diagnose disease; for example, it can be attached to glucose in order to make [¹⁸F]FDG for cancer imaging. The researchers’ new method not only has the potential to improve production of PET radiotracers like FDG, but also to facilitate development of new radiotracers by allowing previously challenging vectors to be radiolabelled in high yields under mild conditions.

“Improving methods for incorporation of fluorine-18 has been a longstanding challenge for the radiotracer community,” said ANSTO’s Dr Benjamin Fraser, a senior author on the study. This is because radio synthesis needs to be performed quickly, efficiently and in high yield, so there is enough radiotracer to scan all patients at a PET medical centre before the radiotracer decays.

“This research is the first example of a rhenium-promoted radio-fluorination — an unprecedented, exciting discovery in the radiochemistry field,” Dr Fraser said.

Dr Fraser explained that a rhenium complex was selected because of its potential for development as a dual-modality PET/optical imaging agent. PET allows diagnosis of tumour location and then optical luminescence guides surgical removal of the tumour.

“The choice of rhenium proved fortuitous for the incorporation of F-18 and was a good example of chance favouring the prepared mind, as the result was not predicted but very significant,” said Dr Fraser.

“It’s also important that the reaction can be done in water, as this simplifies subsequent formulation of the radiotracer in saline for injection into a patient in a clinical setting.”

The study involved the use of microfluidic technologies which “allowed us to optimise all the reaction parameters very quickly”, said Dr Fraser, “such as temperature, time, solvent and additives. We can optimise a given radiolabelling reaction in only three days, which under normal conditions would take one month to complete.

“Another benefit of microfluidics is that we work with only very small amounts of radioactivity,” said Dr Fraser.

As the radiotracer has not yet been tested for use with PET, noted Dr Fraser, the next step is working on conjugating the tracer to new biological vectors, as well as applying the new rhenium method to established radiotracers.

“We can then also investigate its potential use as a dual-modality probe,” he said.