Comparison of imaging using 11C-ITMM and 18F-FDG for the detection of cerebellar ataxia

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Highlights

  • Imaging of mGluR1 has the potential use for estimating cerebellar function.

  • Imaging of mGluR1 was compared with FDG imaging in the cerebellum.

  • Imaging of mGluR1 was comparable to FDG imaging in the cerebellum

  • Imaging of mGluR1 was more strongly associated with the degree of cerebellar ataxia.

  • Imaging of mGluR1 can be a more specific technique for evaluating cerebellar ataxia.

Abstract

Objective

Newly developed methods for imaging type 1 metabotropic glutamate receptor (mGluR1) have the potential use for estimating cerebellar function. We aimed to compare mGluR1 imaging using N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-11C-methoxy-N-methylbenzamide (11C-ITMM) with the existing marker, fluorine-18-labeled fluorodeoxyglucose (18F-FDG) imaging, in the cerebellum.

Methods

Fourteen subjects consisting of 12 patients with cerebellar ataxia and two healthy subjects underwent 11C-ITMM and 18F-FDG positron emission tomography. The degree of ataxia was scored with the Scale for the Assessment and Rating of Ataxia (SARA). Volumes-of-interest were placed on the anterior and posterior lobes and vermis. The binding potential (BPND) was calculated to estimate mGluR1 availability using the white matter as a reference region. 18F-FDG uptake was normalized using the white matter (FUwm).

Results

There were significant positive correlations between the BPND and FUwm values in the anterior lobe (r = 0.83, P < 0.001), posterior lobe (r = 0.69, P = 0.009), and vermis (r = 0.58, P = 0.042). Regarding the relationship of SARA scores with the BPND and FUwm values, a significant negative correlation was found only in the anterior lobe between the SARA scores and BPND values (r =  0.64, P = 0.029).

Conclusion

This study showed that mGluR1 imaging was comparable to 18F-FDG imaging in the cerebellum. However, mGluR1 imaging was more strongly associated with the SARA scores than 18F-FDG imaging was, suggesting that mGluR1 imaging can be a more specific technique than 18F-FDG imaging for evaluating cerebellar ataxia.

Introduction

Recently developed positron emission tomography (PET) imaging of the type 1 metabotropic glutamate receptor (mGluR1) has shown that mGluR1 is exclusively localized in the cerebellar cortex of human brains [1]. This in vivo finding corroborates the evidences from in vitro studies that mGluR1 is predominantly expressed on the dendrites of Purkinje cells facing the synaptic terminals of parallel and climbing fibers [2]. As cerebellar mGluR1 is involved in excitatory neurotransmission, the alteration of mGluR1 expression should theoretically be observed in various cerebellar disorders. Previous studies using small animals have consistently shown that reduction in cerebellar mGluR1 expression is associated with the occurrence of cerebellar ataxia [3], [4], [5], [6]. In a human case of spinocerebellar ataxia type 6 (SCA6), PET imaging of mGluR1 recently confirmed that mGluR1 availability was decreased in the cerebellum [7]. These in vivo and in vitro findings suggest that mGluR1 plays a critical role in the physiology and pathophysiology of Purkinje cells and that mGluR1 imaging can serve as a specific technique for estimating impairment of cerebellar function, as seen in ataxia.

Currently, the most common neuroimaging tools widely used for evaluating cerebellar disorders are fluorine-18-labeled fluorodeoxyglucose (18F-FDG) PET, which provides an index of glucose metabolism, and cerebral perfusion scintigraphy single-photon emission computed tomography (SPECT) [8]. As PET has the advantage of superior image quality over SPECT, 18F-FDG PET is the current standard method for estimating cerebellar function. The aim of this study was to compare mGluR1 imaging with 18F-FDG imaging in the cerebellum and to assess whether mGluR1 imaging can be a more useful technique than 18F-FDG imaging for evaluating cerebellar ataxia. For this purpose, N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl] -4-11C-methoxy-N-methylbenzamide (11C-ITMM) and PET were used to quantify mGluR1 availability. To estimate mGluR1 availability using 11C-ITMM PET, dynamic scanning for > 60 min is required. However, this scanning duration is inconvenient for clinical use and for subjects with some types of cognitive or physical disabilities. Therefore, we additionally examined whether a more simplified protocol, late-phase static imaging, can be an alternative to dynamic imaging.

Section snippets

Research participants

The study was conducted in accordance with the Helsinki Protocol and approved by the Ethics Committee of the Tokyo Metropolitan Institute of Gerontology. Written informed consent was obtained from all participants. The participants consisted of 14 subjects (6 men and 8 women; aged 64.0 ± 15.9 years [mean ± SD]) who were recruited from ongoing studies on mGluR1 and neurodegenerative disorders at our institute [9] and had completed both 11C-ITMM and 18F-FDG PET scans. Twelve were patients with

Results

The values of BPND, BPEq, FUwm, and FUgn, and the relationships among BPND and the other variables are shown in Table 1 and Fig. 1, respectively. After the Bonferroni adjustment, there were significant positive correlations between the BPND and BPEq values (Fig. 1A) in the anterior lobe (correlation coefficient: r = 0.96, P < 0.001), posterior lobe (r = 0.90, P < 0.001), and vermis (r = 0.92, P < 0.001), and between the BPND and FUwm values (Fig. 1B) in the anterior lobe (r = 0.83, P < 0.001), posterior lobe (r

Discussion

The primary objective of this study was to compare cerebellar mGluR1 images with 18F-FDG images to assess which imaging technique was better for evaluating cerebellar ataxia. As there is no consensus on the most suitable reference region in 18F-FDG images for intersubject comparison, investigators must specify the reference region depending on the target regions and study design. We used 2 types of normalized 18F-FDG images to quantify 18F-FDG uptake in the cerebellum and compare with

Conclusions

This study showed that there were positive correlations between the BPND and FUwm values and that mGluR1 imaging was comparable to 18F-FDG imaging in the cerebellum. However, regarding the relationships of the SARA scores with BPND and FUwm values, mGluR1 imaging was more strongly associated with the degree of cerebellar ataxia than 18F-FDG imaging was, suggesting that mGluR1 imaging can be a more specific technique than 18F-FDG PET imaging for evaluating cerebellar ataxia.

Disclosure

None of the authors has any conflict of interest to disclose.

Acknowledgements

This study was supported by a Grant-in-Aid for Young Scientists (B) No. 15K19503 to Ishibashi and for Scientific Research (B) No. 24390298 to Ishiwata from the Japan Society for the Promotion of Science and by Takeda Science Foundation to Ishibashi.

References (21)

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