PET imaging of noradrenaline transporters in Parkinson’s disease: focus on scan time

Abstract

Objective In subjects with idiopathic Parkinson’s disease (PD) the functional state of the locus coeruleus and the subtle derangements in the finely tuned dopamine–noradrenaline interplay are largely unknown. The PET ligand ( S,S )-[ 11 C]- O -methylreboxetine (C-11 MRB) has been described to reliably bind noradrenaline transporters but long scanning protocols might hamper its use, especially in patients with PD. We aimed to assess the feasibility of reducing C-11 MRB scans to 30 min. Methods Ten patients with idiopathic PD underwent dynamic C-11 MRB PET (120 min duration) and brain magnetic resonance imaging. Model-based (i.e., simplified and multilinear reference tissue model 2) non-displaceable binding potentials (BP) of selected brain regions were analyzed for a 90 min scan protocol and compared with BP derived from static 30-min data with different starting times (30, 40, 50 and 60 min) after C-11 MRB injection. Intraclass correlation coefficient and linear regression analysis were used to explore the association between BP of different scan durations. Spearman’s ρ served to describe the correlation of BP with demographic and clinical parameters. Results With respect to kinetic models, BP 50–80 and BP 60–90 showed the best correlation in several brain areas ( R 2 range 0.95–98; p < 0.001). The thalamus showed the highest BP on average. No correlation between BP, clinical and demographic characteristics was observed. Conclusions An acquisition time of 30 min, starting 50 or 60 min after C-11 MRB injection, allows a reliable estimation of noradrenaline transporter binding values in Parkinsonian people. A short acquisition time can significantly reduce the discomfort of Parkinsonian patients and facilitate PET studies, especially in the medication-off-state.

Recent advances in radiotracers targeting norepinephrine transporter: structural development and radiolabeling improvements

“…The potential of evaluating PD patients using 11 C-MRB PET has been confirmed, and the imaging protocol has been optimized following the investigation of kinetic models. An acquisition time of 30 min after 50 or 60 min of tracer injection allows for a reliable estimation of NET, which can significantly reduce the discomfort of PD patients (Brumberg et al 2019). Lastly, in addition to the above applications, 11 C-MRB has also been used to investigate noradrenergic activation and modulation in different regions of the brain in response to insulin-induced hypoglycemia (Belfort-DeAguiar et al 2018).…”

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Locus Coeruleus Modulates Neuroinflammation in Parkinsonism and Dementia

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