Fluorodopa PET

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Edward Garnett, Gunther Firnau and Claude Nahmias, Hamilton, Canada (McMaster University Medical Centre is their affiliation on a 1995 paper; the 1983 byline was not read). Nature 305:137–138, 1983.

What happened

Dopamine is hard to image directly. The team labelled L-dopa, which the brain converts to dopamine, with fluorine-18, a positron-emitting atom, and scanned healthy volunteers with positron emission tomography (PET). The tracer collected specifically in the dopaminergic pathways of the basal ganglia, and its turnover could be measured without surgery. The abstract describes this as the first demonstration of the regional distribution of a neurotransmitter in the conscious human brain.

This paper studied normal volunteers. Reduced uptake in Parkinson's came in a follow-up by the same group (Garnett, Nahmias, Firnau, Can J Neurol Sci 1984): in six patients with hemiparkinsonism (one-sided signs) striatal accumulation was reduced on the side opposite the symptoms, especially in the putamen, compared with five controls.

Why it moved us toward a cure

Dopamine loss (landmark 1) could now be seen and quantified in life, not only at autopsy. That is the basis for later imaging endpoints and for using DAT scans to select trial participants (landmark 79). A real brain-chemistry measure is also what lets a trial test whether a drug slows loss, not only whether symptoms ease.

Outcome

Advanced. The idea of imaging dopamine terminals in life carried on in later dopamine imaging (landmark 79). The 1983 paper does not itself show disease change.

Sources

• Garnett, Firnau & Nahmias, Nature 1983;305:137–138, DOI 10.1038/305137a0 (abstract via Europe PMC, PMID 6604227)
• Garnett, Nahmias & Firnau, "Central dopaminergic pathways in hemiparkinsonism examined by positron emission tomography", Can J Neurol Sci 1984;11:174-179, DOI 10.1017/s0317167100046369, PMID 6608982 (abstract)
• Not yet verified: whether 1984 was the first PET study in Parkinson's patients; the number of volunteers in the 1983 paper; how widely fluorodopa PET is used in trials today.