PET imaging of dopamine transporters with [18F]FE-PE2I: Effects of anti-parkinsonian drugs

Abstract

Purpose: [18F]FE-PE2I is a promising radioligand for dopamine transporter (DAT) imaging. This study aimed to determine any correlation between striatal [18F]FE-PE2I binding and immunohistochemical (IHC) stain of tyrosine hydroxylase (TH) in the striatum, and to evaluate the effects of therapeutic drugs on [18F]FE-PE2I binding. Materials and Methods: Dynamic PET/CT of [18F]FE-PE2I was performed on Parkinsons disease (PD) rat models, induced by unilateral injection of 6-OHDA into the striatum. A simplified reference tissue model using the cerebellum as a reference was used to calculate the striatal binding potential (striatal BPND). Ratio of optical density (OD) of TH-reactive fibers in the PD and normal rats was correlated with ratio of striatal BPND. To study therapeutic drug effects, each of the 4 normal rats were pretreated with L-DOPA combined with benserazide, pramipexole, amantadine and escitalopram 30 min before [18F]FE-PE2I injection. The L-DOPA/benserazide effect on lesioned and unlesioned striatal BPND was also assessed in the PD rats.

Results: The BPND was significantly lower in the lesioned striatum than in the unlesioned one or the striatum of normal rats. The ratio of OD of TH-reactive fibers linearly correlated with the ratio of striatal BPND (r=0.741, P<0.05). After the pre-treatment with pramipexole, amantadine and escitalopram, the values of striatal BPND did not differ from those of control rats. However, pre-treatment of L-DOPA/benserazide significantly reduced the striatal BPND (P=0.03). The striatal BPND of PD rats with L-DOPA/benserazide was not different from those of same PD rats with placebo (normal saline) treatment. For midbrain binding, pretreatment of escitalopram did not affect the midbrain BPND on normal rats.

Conclusion: [18F]FE-PE2I may be used as a radioligand for in vivo imaging of the DAT. In normal rats, [18F]FE-PE2I binding is unaffected by therapeutic drugs for PD including pramipexole, amantadine and escitalopram. L-DOPA/benserazide does not affect the striatal [18F]FE-PE2I binding in PD rats.