Dual phase 18F-FP CIT PET and 99mTc- ECD SPECT findings of Huntington's disease.

Fluorine-18 N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane (18F- FP CIT) has been used for the differential diagnosis of atypical parkinsonian disorders, and Technetium 99m ethyl cysteinate dimer (99mTc- ECD) has been used for evaluation of cerebral blood flow. A 60-year-old female with a history of Huntington's disease (HD) with full mutation of cytosine-adenine-guanine (GAG) 18/43 repeats underwent early and late 18F- FP CIT positron emission tomography/computed tomography (PET/CT) and 99mTc- ECD single-photon emission computed tomography (SPECT). The 18F-FP CIT PET/CT showed decreased uptake in both basal ganglia, both frontal and parietotemporal lobes at early images, and decreased presynaptic dopamine transporter (DAT) binding in both ventral & posterior putamen at late images. 99mTc- ECD SPECT showed decreased perfusion in both basal ganglia, both frontal and temporal lobes. Early 18F- FP CIT PET/CT and 99mTc- ECD SPECT images showed similar findings in Huntington's disease.

Introduction

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder containing an amplified number of (CAG)n trinucleotide repeats and pathologically characterized by neuronal loss and neuroreceptor alterations in the striatum, including a reduction in dopamine receptor density. The clinical picture includes motor impairments, cognitive dysfunction, personality change, and susceptibility to mental disorders [1-5].

Early FP CIT imaging reflects perfusion and Laere et al. [6] reported that dual-tracer DAT imaging and perfusion SPECT in combination with discrimination analysis allowed accurate differentiation of the most common forms of Parkinsonism. No direct comparative study of 99mTc-ECD perfusion SPECT and early phase (perfusion) 18F-FP-CIT PET has been performed in Huntington's disease, though they are considered to be well correlated because both reflect perfusion. In the present case, the author compared perfusion 18F-FP-CIT PET/CT and 99mTc-ECD perfusion SPECT in a patient with HD.

Case presentation

A 60-year-old woman with a history of the left hand and leg tremors complained of gait disturbance about 10 years ago and symptoms more progressed. Abnormal behavior and psychotic symptoms also developed. She had a full mutation of cytosine-adenine-guanine (CAG) 18/43 repeats via polymerase chain reaction (PCR) and fragment analysis. Previous studies reported that loss of presynaptic terminals or a reduced expression of dopamine transporter in the nigrostriatal dopaminergic system in Huntington's disease [2]. Both atrophy and loss of substantia nigra neurons have been reported to occur in HD and found that a significant nigrostriatal dysfunction does occur in HD as assessed by means of 123I-FP-CIT SPECT [3,7]. She underwent 18F- FP CIT PET/CT for the differentiation of parkinsonism. Antiparkinsonian drugs has been stopped 12 hours before the scan and perfusion image acquisition was performed within 10 minutes of intravenously injecting 185 MBq of 18F- FP CIT. Late 18F- FP CIT PET/CT images were obtained 3 hours after intravenous injection to assess striatal DAT binding patterns (Fig. 1). Early 18F-FP CIT PET/CT showed decreased uptake in the both basal ganglia, both frontal and parietotemporal lobes (A). Decreased presynaptic DAT binding in both ventral & posterior putamen at late MIP and transaxial images (B, C). 99mTc-ECD SPECT images were obtained 30 minutes after injecting 99mTc- ECD 925 MBq (25 mCi) using a SPECT camera. Patient was imaged in a standardized manner (supine, dimly lit room, low noise). 99mTc-ECD SPECT images showed decreased perfusion in both basal ganglia, both frontal and temporal lobes. (Fig. 2).

Fig. 1

Early (A) and late (B, C)18F- FP CIT PET/CT images were obtained10 minutes and 3 hours after intravenous injection to assess striatal DAT binding patterns.Early 18F-FP CIT PET/CT showed decreased uptake in both basal ganglia, both frontal and parietotemporal lobes. Decreased presynaptic DAT binding in both ventral & posterior putamen at late MIP (maximum intensity projection)and transaxial images.

Fig. 2

99mTc-ECD SPECT images showed decreased perfusion in both basal ganglia, both frontal and temporal lobes at transaxial images.

Discussion

Brain metabolism, postsynaptic dopaminergic function, and phosphodiesterase 10A levels were proven to be powerful in assessing disease progression. However, no single technique may be currently considered an optimal biomarker and an integrative multimodal imaging approach combining different techniques should be developed in HD [4]. 18F-FP-CIT PET shows a rapid tracer uptake increase in the brain and early perfusion uptake of FP CIT in dopamine-poor regions (e.g., cerebral cortex and cerebellum) peaks around 10 minutes after injection [8]. Furthermore, early imaging within 10 minutes of injecting 18F-FP-CIT well represents perfusion flow and mimics glucose metabolism in the brain. The presence of striatal hypometabolism is a consistent finding in HD patients, who also show reduced cortical cerebral metabolic rate of glucose (CMRglc), involving in particular, the frontal and temporal lobe [9] and our case shows decreased uptake in both basal ganglia, both frontal and parietotemporal lobes at early perfusion FP CIT images.

Perfusion imaging with ECD or HMPAO may also be helpful because regional cerebral perfusion is usually coupled to cerebral metabolism [10,11]. Previous studies reported that Huntington patients have bilaterally decreased uptake of 99mTc-d,l-hexamethylpropyleneamine oxime (HMPAO) brain perfusion SPECT in the basal ganglia regions involving the heads of the caudate nuclei and adjacent structures, which reflects decreased neuronal function [5,12]. Also reported decreased uptake in caudate and lentiform nuclei and in the cerebral cortex, especially in the frontal and parietal areas [13]. Accurate diagnoses often require FDG PET or perfusion SPECT and DAT imaging, but there are inconveniences, such as the radiation exposures and high costs involved [8].

Accordingly, the present case showed perfusion FP CIT PET/CT uptake was similar to cerebral perfusion ECD SPECT uptake, a single tracer dual-phase FP CIT PET test might help the differentiation of HD.

Patient consent

Informed consent was obtained.