Quantification of striatal vesicular monoamine transporters in the human brain with [18F]AV133

  • Prof Christopher Rowe, Dept of Nuclear Medicine and Centre for PET, Austin Health, Australia
  • Dr Rajinder Dhamija, Dept of Neurology, Austin Health, Australia
  • A/Prof John Drago, Howard Florey Institute, University of Melbourne, Australia
  • Dr Rachel Mulligan, Department of Nuclear Medicine, Centre for PET, Austin Health, Australia
  • Ms Svetlana Pejoska, Department of Nuclear Medicine, Centre for PET, Austin Health, Melbourne, VIC, Australia
  • Dr Daniel Skovronsky, Avid Radiopharmaceuticals, Inc., United States
  • Prof Hank Kung, Dept of Radiology, University of Pennsylvania, United States
  • Dr Victor Villemagne, Dept of Nuclear Medicine and Centre for PET, Austin Health, Australia

    • Background: Vesicular monoamine transporter type 2 (VMAT2) imaging with 11C-DTBZ has proven useful for the evaluation of monoaminergic terminals in vivo with PET. However, the 20 min half-life of C-11 restricts the use of 11C-DTBZ to PET centres with on-site cyclotron. The aim of this study was to assess 18F-AV133, a novel VMAT2 binding ligand, in Parkinson’s disease (PD) patients, age-matched healthy controls (HC), as well as in dementia with Lewy Bodies (DLB) and Alzheimer’s disease (AD).

    Methods: Twenty-two participants (10 PD; 7 HC, 4 DLB and 1 AD) underwent PET imaging after iv injection of 250 MBq of 18F-AV133. Distribution volume ratios (DVR) were calculated through graphical analysis using a reference tissue model with the primary visual cortex as input function.

    Results: Significantly lower striatal DVRs were observed in PD (1.74 ± 0.46) when compared with HC (3.0 ± 0.20; p<0.001, effect size = 5.7). VMAT2 reductions were greatest in posterior putamen (-55%) than in anterior putamen (-45%) or caudate nuclei (-25%). Similar reductions were observed in DLB patients. Both HC and AD scans were clearly distinguishable from PD subjects.

    Conclusions: Our results show that striatal VMAT2 can be quantified in vivo with 18F-AV133. The longer half-life of F-18 will allow for wider application of monoaminergic imaging with PET in a variety of neurodegenerative and neurotoxic conditions, allowing better differential diagnosis and treatment monitoring.