WMIC: FMT-PET monitors gene expression in Parkinsons disease

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6-18F-fluoro-L-m-tyrosine (FMT)-PET is a valuable technique to monitor the expression of aromatic L-amino acid decarboxylase (AADC), as part of the assessment of long-term in vivo gene therapy in Parkinson’s disease, according to a presentation at the World Molecular Imaging Conference (WMIC) in Kyoto, Japan.

A severe loss of the nerve terminals in advanced Parkinson’s disease is associated with an 80-95 percent depletion of AADC. It has previously been demonstrated that the recombinant adenoassociated virus vector-mediated gene transfer of AADC into the striatal neurons in combination with the oral administration of L-dopa has lead to the behavioral recovery in primate models of Parkinson’s disease, according to Sayaka Asari, MD, from the division of neurology, department of medicine at Jichi Medical University in Shimotsuke, Japan.

In the study, Asari and colleagues performed FMT-PET to evaluate the expression of the transgene in a phase 1 clinical trial of AADC gene therapy.

Asari and colleagues hypothesized that, a non-catecholic tracer, FMT for PET is a good substrate for AADC since it is not metabolized by catechol-O-methyl-transferase, and it therefore has a better sensitivity than the more commonly used L-dopa.

Six patients, ranging from 51 to 68 years of age, comprising of four men and two women, and presenting with moderate to advanced Parkinson's disease (Hoehn & Yahr Stage IV), received adenoassociated virus vectors expressing human AADC via bilateral intraputaminal infusions, according to Asari.

The researchers evaluated the six patients at baseline pre-operative and thereafter monthly post-operatively for six months, using multiple measures, including the Unified Parkinson’s disease Rating Scale, motor state diaries and FMT-PET. For PET assessment, all patients stopped taking dopaminergic medications at least six hours before and all took an oral peripheral AADC inhibitor, one hour before the FMT injection. The radioactivities within the volumes of interest drawn in the putamen and occipital lobe were calculated between 80 and 90 minutes after the tracer injection.

Six months after surgery, the motor functions in the off medication state improved an average of 46 percent based on the Unified Parkinson’s Disease Rating Scale scores. Motor diaries showed increased “on-state” even though the dose of L-dopa was not observed to increase, according to Asari and colleagues.

The FMT activity increased at four weeks postoperatively, and the mean increase at six months was 56 percent. Three patients who underwent PET scans 24 months after surgery showed a persistently increased FMT uptake.

“FMT-PET is therefore considered to be a valuable technique to image the AADC distribution in Parkinson's disease,” concluded Asari and colleagues.