Radiotracer May Improve Differential Diagnosis of Parkinson’s

An interdisciplinary team of researchers has developed a substance that may improve the differential diagnosis of Parkinson’s disease based on brain imaging — potentially allowing physicians to distinguish between patients who are sensitive to the side effects of parkinsonian medications and those who are not.

Levodopa is one of the main medications used to alleviate the symptoms of Parkinson’s disease. However, when administered for long periods of time, it causes significant side effects.

A major challenge that doctors face when treating Parkinson’s patients is the lack of a specific test to determine whether a patient is sensitive to the side effects of parkinsonian medications. Instead, doctors must rely on certain symptoms for diagnosis, such as motor dysfunction.

“[W]e don’t yet have a suitable method for differential diagnosis, i.e. to detect at early stage whether a patient is sensitive to the side effects,” chemist Thu Hang Lai, PhD, a researcher on the project, said in a press release.

Lai is part of the research team at the Institute of Radiopharmaceutical Cancer Research, at Helmholtz-Zentrum Dresden-Rossendorf (HZDR) in Germany, that has now developed a method to aid in the differential diagnosis of Parkinson’s — a radiotracer molecule called [18F]FLUDA.

Radiotracers are compounds prepared with radioactive elements that are used for medical applications. These compounds emit radioactivity which allows them to be detected by positron emission tomography (PET) scans.

A PET scan is an imaging technique that uses small amounts of radioactive materials, a special camera, and a computer to help detect emitted radiation and image biological function in vivo.

[18F]FLUDA was specifically designed to attach itself to receptors in the brain called adenosine receptors. Adenosine is a neurotransmitter (chemical molecule) that is used to send signals between nerve cells in the brain and allows them to communicate. When adenosine attaches to an adenosine receptor, the whole nerve cell slows down. Caffeine, for example, has a similar molecular structure to adenosine and as such can bind to its receptors, blocking adenosine from performing its function and producing the stimulating effect of caffeine-containing beverages such as coffee and tea.

When [18F]FLUDA attaches itself to adenosine receptors, it can be detected by PET scans. This means that the areas of the brain that reflect increased radioactivity have a higher density of adenosine receptors and can be monitored.

So far, [18F]FLUDA performed well in pre-clinical experiments. The radiotracer was stable, readily detected in PET scans, did not suffer any degradation on its way to the brain, and did not show significant toxicity when tested in animal models. Radiation protection studies also showed positive results.

“With a suitable radiopharmaceutical for use in humans, we hope to be able to make correct differential diagnoses and thus differentiate between Parkinson’s patients who are sensitive to side effects and those who are not,” said team member Rodrigo Teodoro, PhD.

The team now wants to test its radiotracer in clinical trials. The researchers have already filed for a patent, but the first step in proving the usefulness of [18F]FLUDA will be to demonstrate its safety and effectiveness in healthy volunteers and in Parkinson’s patients. They are currently looking for a clinical partner to aid with these trials.

This discovery has won the team HZDR’s Innovation Contest.