Parkinson's disease에서 [18F]-FP-CIT을 이용한 Brain PET/CT영상의 유용성

강용길 ; 홍시영 김천대학교 2009 김천대학교 논문집 Vol.30 No.-

Neuroreceptors and transporters have an important role in brain function.Parkinson's disease is a common neurodegenerative disorder that is mainly causedby dopaminergic neuron loss in the substantia nigra.Distribution, density, and activity of neuroreceptors and transporters can bevisualized by radiotracers with PET and SPECT.In vivo PET and SPECT imaging of presynaptic dopamine imaing are alreadyapplied to Parkinson's disease and other parkinsonism, and can demonstrate thedopaminergic dysfunction.Dopamine transporter imaging is useful in the diagnosis of Parkinson's diseaseand the most successful technique in the clinical use of neuroreceptor imaging.​Recently, several radiopharmaceuticals including 123I-FP-CIT, 99mTc-TRODATand 18F-FP-CIT for dopamine transporter imaging have been approved for theroutine clinical use in several European countries, Taiwan and Korea, respectively.Therefore, In this paper an overview of Parkinson's disease medicines for diag-nosis and radioactive 18F-FP-CIT using a PET/CT imaging has confirmed theusefulness of the clinical use.

Spatial Normalization Using Early-Phase [18F]FP-CIT PET for Quantification of Striatal Dopamine Transporter Binding

배성우,최홍윤,위원석,팽진철,천기정,강건욱,이동수 대한핵의학회 2020 핵의학 분자영상 Vol.54 No.6

Purpose The precise quantification of dopamine transporter (DAT) density on N-(3-[18F]Fluoropropyl)-2β-carbomethoxy- 3β-(4-iodophenyl) nortropane positron emission tomography ([18F]FP-CIT PET) imaging is crucial to measure the degree of striatal DAT loss in patients with parkinsonism. The quantitative analysis requires a spatial normalization process based on a template brain. Since the spatial normalization method based on a delayed-phase PET has limited performance, we suggest an early-phase PET-based method and compared its accuracy, referring to the MRI-based approach as a gold standard. Methods A total of 39 referred patients from the movement disorder clinic who underwent dual-phase [18F]FP-CIT PET and took MRI within 1 year were retrospectively analyzed. The three spatial normalization methods were applied for quantification of [18F]FPCIT PET-MRI-based anatomical normalization, PET template-based method based on delayed PET, and that based on early PET. The striatal binding ratios (BRs) were compared, and voxelwise paired t tests were implemented between different methods. Results The early image-based normalization showed concordant patterns of putaminal [18F]FP-CIT binding with anMRI-based method. The BRs of the putamen from the MRI-based approach showed higher agreement with early image- than delayed imagebased method as presented by Bland-Altman plots and intraclass correlation coefficients (early image-based, 0.980; delayed image-based, 0.895). The voxelwise test exhibited a smaller volume of significantly different counts in putamen between brains processed by early image and MRI compared to that between delayed image and MRI. Conclusion The early-phase [18F]FP-CIT PET can be utilized for spatial normalization of delayed PET image when theMRI image is unavailable and presents better performance than the delayed template-based method in quantitation of putaminal binding ratio.

Imaging Procedure and Clinical Studies of [ 18 F]FP-CIT PET

성창환 대한핵의학회 2024 핵의학 분자영상 Vol.58 No.4

N-3-[18F]fluoropropyl-2β-carbomethoxy-3β-4-iodophenyl nortropane ([18F]FP-CIT) is a radiopharmaceutical for dopaminetransporter (DAT) imaging using positron emission tomography (PET) to detect dopaminergic neuronal degeneration inpatients with parkinsonian syndrome. [18F]FP-CIT was granted approval by the Ministry of Food and Drug Safety in 2008as the inaugural radiopharmaceutical for PET imaging, and it has found extensive utilization across numerous institutions inKorea. This review article presents an imaging procedure for [18F]FP-CIT PET to aid nuclear medicine physicians in clinicalpractice and systematically reviews the clinical studies associated with [18F]FP-CIT PET.

Evaluation method based non-invasive imaging in Parkinson’s disease models

Yiseul Choi,Eun Sang Lee,Jang Woo Park,Youn Kyoung Jeong,Mijeong Park,Hye Kyung Chung 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

Parkinson’s disease (PD) is the second most common neurodegenerative movement disorder and is characterized by the loss of dopaminergic neurons in the nigrostriatal system. To monitor the PD, PET with [18F]FP-CIT for the dopamine transporter (DAT) has become a widely used tool. For PD study, invaluable tools are neurotoxin-based animal models. To validate the usefulness of these animal models in DAT imaging, we discuss the evaluation of these models. To develop most classical neurotoxin PD animal models, we injected 6-hydroxydopamine (6-OHDA) into the substantia nigra of mouse or treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by oral routes. After that, [18F]FP-CIT PET imaging were acquired. The changes in [18F]FP-CIT uptake were also analyzed using PMOD software. For analysis of 6-OHDA induced PD model, we used [18F]FP-CIT binding ratio observed in the right/left striatum of the mice. Ratio average of 6-OHDA induced group was 0.477 as compare with control group ratio average 0.987. When MPTP-induced PD model were analyzed by [18F]FP-CIT binding ratio in the average of left and right striatum with the cerebellum as a reference, MPTP-treated group was 1.944 compared to average of the control group ratio 2.924. In conclusion, the evaluation of each PD model with non-invasive imaging has shown to be a valuable objective of PD research. In the future, these analyzes to preclinical drug evaluation may be suitable for development of new treatment.

Longitudinal Decline of Striatal Subregional [18F]FP-CIT Uptake in Parkinson’s Disease

성창환,이재현,오정수,오민영,이상주,오승준,정선주,이종식,김재승 대한핵의학회 2017 핵의학 분자영상 Vol.51 No.4

Purpose Dopamine transporter imaging is suggested to be a useful imaging biomarker for Parkinson’s disease (PD) progression and monitoring drug effects.We investigated the longitudinal decline characteristics of striatal [18F]FP-CIT uptake in PD. Methods We retrospectively reviewed 35 PD patients and 9 non-PD patients. All patients underwent [18F]FP-CIT PET at the initial diagnosis and follow-up. PET images were spatially normalized and analyzed with eight striatal and one occipital VOI templates. We measured the specific to non-specific binding ratio (SNBR) of the striatal subregions and calculated the absolute annual reduction (AAR) and relative annual reduction (%RAR) of the SNBRs. Results Total striatal SNBRs in PD patients were significantly lower than those in non-PD patients, with the most significant difference in the posterior putamen. Both AAR (0.26 ± 0.14 vs. 0.09 ± 0.19, p < 0.05) and %RAR (6.9 ± 3.5 vs. 1.2 ± 2.7, p < 0.001) of total striatal SNBRs were significantly greater in PD than non-PD patients. There were no significant differences in the AAR and %RAR of total striatal SNBRs between elderly and young onset PD. The AARs of the posterior putamen were higher in early PD than in advanced PD. Conversely, the %RARs were not significantly different between early and more advanced PD. The disease duration was significantly negatively correlated with the AAR but not with the %RAR of the posterior putamen. Conclusions The longitudinal decline of striatal [18F]FP-CIT uptake in PD was nonlinear and significantly faster than that in non-PD, with a different rate of decline among the striatal subregions.

18F-FP-CIT Positron Emission Tomography for Correlating Motor and Cognitive Symptoms of Parkinson’s Disease

양영순,천미주,곽용태 대한치매학회 2017 Dementia and Neurocognitive Disorders Vol.16 No.3

Background and Purpose The aim of this paper was to investigate the utility of 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4iodophenyl) nortropane (FP-CIT) positron emission tomography (PET) for evaluating the severity of Parkinson’s disease (PD) according to various clinical stages, and to identify the relationship between the striatal substructure and the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score, cognitive symptoms through 18F-FP-CIT PET. Methods We retrospectively identified 542 patients with various clinical stages of PD who underwent an 18F-FP-CIT PET at our clinics. The difference between the 18F-FP-CIT PET according to the Hoehn-Yahr stage, correlation between 18F-FP-CIT PET and the UPDRS III grouped motor items, and the Korean Mini-Mental State Examination (K-MMSE) were investigated. Results As disease progressed, the right caudate and both the anterior putamen and caudate/putamen ratios exhibited a significantly lower uptake. The uptake of all striatal substructures was significantly correlated with the UPDRS total motor score. The right caudate nucleus was significantly related to both the UPDRS tremor items and the right UPDRS akinesia-rigidity items. The left caudate nucleus was related to both the UPDRS tremor items and UPDRS akinesia-rigidity items. The right anterior putamen was related to the axial items, right tremor and akinesia-rigidity items; while the left anterior putamen was related to the right tremor and right akinesia-rigidity items. Both of the posterior putamens were related to the axil items, left tremor and left akinesia rigidity items. K-MMSE was not significantly related to any striatal substructures. Conclusions The UPDRS total motor score was significantly correlated with the uptake of all striatal substructures. However, the 18F-FPCIT uptake in specific striatal substructures was rather complexly correlated with the UPDRS motor grouped items and was not significantly related to K-MMSE. These results suggest the possibility of the complex pathophysiology of motor symptoms of PD and limitation of 18F-FPCIT PET for the evaluation of the severity of PD motor and cognitive symptoms.

The Study of Radiation Exposure Reduction by Developing Corpus Striatum Phantom

Kim Jung-Soo(김정수),Park Chan-Rok(박찬록) 대한방사선과학회(구 대한방사선기술학회) 2017 방사선기술과학 Vol.40 No.4

본 연구는 파킨슨질환의 진행 정도를 평가할 수 있는 선조체를 모사한 brain 팬텀을 직접 제작하여, PET-CT검사 시 최적의 영상의 질을 유지하면서 CT 스캔에 의한 brain 선량 저감을 위한 가능성을 평가하였다. 팬텀의 hot sphere와 background (rad oact v ty rat o 3:1)에 18F FP-CIT를 주입하고, 관전압(100, 120kVp)과 관전류(80, 140, 200 mAs)의 조건을 변화시키며 CT 스캔을 실험하였다(기준조건; 120 kVp, 140mAs). 각 조건에 따라 예상유효선량을 conversion factor를 적용해 계산하였고, SNR과 CRChot의 영상평가 인자를 설정하여 영상의 질을 평가하였다. 실험결과 CT 촬영 기준조건 이하에서의 예상유효선량은 최소 10% 에서 최고 60% 정도 감소하였고, 기준조건 이상에서의 예상유효선량은 40% 증가하였다. 또한 PET 영상의 SNR과 CRChot의 유의한 차이는 없었으므로, 관전압과 관전류의 감소에 따라 brain 선량이 감소함을 확인하였다. 이와 동시에 스캔 조건의 변화에도 불구하고 SNR과 CRChot 측면에서의 영상의 질에는 유의한 변화가 없었다. 이러한 사실은 낮은 선량 조건으로도 기존의 선량 조건으로 획득한 영상의 질 수준을 얻을 수 있었으므로, 추후 brain PET-CT 스캔의 선량감소와 동시에 영상의 질 향상에 관한 연구의 기초자료로 활용이 가 능할 것으로 사료된다. The study is to produced a brain phantom simulating corpus striatum, which can evaluate the progression of parkinson s disease, to investigate possibility of reducing the brain exposure dose to CT while maintaining opti-mal image quality during PET-CT examinations. CT scans were performed by varying tube voltage (100, 120 kVp) and tube current (80, 140, 200 mAs) with 18F FP-CIT injected into the phantom s hot sphere and back-ground (radioactivity ratio 3:1)(reference condition; 120 kVp, 140 mAs). Estimated effective dose was calculated by using conversion factor according to each condition, and image quality was evaluated by setting SNR and CRChot image evaluation factors. Experimental results showed that the predicted effective dose below the CT imaging reference condition was reduced by at least 10% and by up to 60%, and the predicted effective dose beyond the reference condition was increased by 40%. In addition, there was no significant difference between SNR and CRChot of PET images, and it was confirmed that brain dose decreased with decrease of tube voltage and tube current. At the same time, there was no significant change in the quality of the image in terms of SNR and CRChot despite the change in scan conditions. This fact suggests that the quality of the images ac-quired under the existing dose conditions can be obtained even at low dose conditions and it is expected that it will be possible to use the brain PET-CT scan as a basic data for the research on reduction of dose and improvement of image quality.

Differential Diagnosis of Patients with Inconclusive Parkinsonian Features Using [18F]FP-CIT PET/CT

박은경,황유미,이찬녕,김수진,오선영,김영철,최재걸,박건우 대한핵의학회 2014 핵의학 분자영상 Vol.48 No.2

Purpose It is often difficult to differentiate parkinsonism,especially when patients show uncertain parkinsonian features. We investigated the usefulness of dopamine transporter(DAT) imaging for the differential diagnosis of inconclusiveparkinsonism using [18F]FP-CIT PET. Methods Twenty-four patients with inconclusive parkinsonianfeatures at initial clinical evaluation and nine healthycontrols were studied. Patients consisted of three subgroups:nine patients whose diagnoses were unclear concerningwhether they had idiopathic Parkinson’s disease or druginducedparkinsonism (‘PD/DIP’), nine patients who fulfilledneither the diagnostic criteria of PD nor of essential tremor(‘PD/ET’), and six patients who were alleged to have eitherPD or atypical parkinsonian syndrome (‘PD/APS’). BrainPET images were obtained 120 min after injection of185 MBq [18F]FP-CIT. Imaging results were quantified andcompared with follow-up clinical diagnoses. Results Overall, 11 of 24 patients demonstrated abnormallydecreased DAT availability on the PET scans, whereas 13were normal. PET results could diagnose PD/DIP and PD/ET patients as having PD in six patients, DIP in seven, and ETin five; however, the diagnoses of all six PD/APS patientsremained inconclusive. Among 15 patients who obtained afinal follow-up diagnosis, the image-based diagnosis wascongruent with the follow-up diagnosis in 11 patients. Fourunsolved cases had normal DAT availability, but clinicallyprogressed to PD during the follow-up period. Conclusion [18F]FP-CIT PET imaging is useful in the differentialdiagnosis of patients with inconclusive parkinsonianfeatures, except in patients who show atypical features orwho eventually progress to PD.

Is Parkinson’s Disease with History of Agent Orange Exposure Different from Idiopathic Parkinson’s Disease?

양영순,천미주,곽용태 대한치매학회 2016 Dementia and Neurocognitive Disorders Vol.15 No.3

Background and Purpose During Vietnam War, many Korean soldiers were dispatched to fight in the war where they were exposed toAgent Orange. Until now, there exist only limited evidence on existence of association between exposure to Agent Orange and Parkinson’sdisease (PD). To elucidate the effects of Agent Orange exposure on PD, we compared the clinical characteristics and radiolabeled 18F-FP-CITPET uptake between patients with Agent Orange exposure and patients with Agent Orange no-exposure. Methods We retrospectively evaluated 143 patients exposed to Agent Orange and 500 patients with no exposure to Agent Orange from ourmovement clinics database. The differences between clinical characteristics and pattern of 18F-FP-CIT PET uptake were investigated. Results Among Unified Parkinson’s Disease Rating Scale III motor subscales, tremor at rest, rigidity, finger taps, and rapid alternatingmovement was significantly higher in patients exposed to Agent Orange as compared to patients with no exposure to Agent Orange. The facialexpression score was significantly lower in patients exposed to Agent Orange as compared to patients with no exposure to Agent Orange. Compared to patients not exposed to Agent Orange, all basal ganglia areas (contra- and ipsilateral caudate nucleus, anterior putamen, andposterior putamen) showed a lower18F-FP-CIT uptake and higher asymmetry index of anterior and posterior putamen was found in patientsexposed to Agent Orange. The caudate/putamen ratio was significantly lower in patients exposed to Agent Orange as compared to patientswith no exposure to Agent Orange. Conclusions This study showed a different clinical profile and FP-CIT PET findings between patients exposed to Agent Orange as comparedto patients with no exposure to Agent Orange. This finding suggests the possibility of different pathophysiology of PD in patients exposedto Agent Orange from idiopathic PD.

Evaluation of Therapeutic Efficacy using [18F]FP-CIT in 6-OHDA-induced Parkinson's Animal Model

박장우,Yi Seul Choi,김동현,이은상,박찬우,정혜경,유란지 대한방사성의약품학회 2023 Journal of radiopharmaceuticals and molecular prob Vol.9 No.1

Parkinson's disease is a neurodegenerative disease caused by damage to brain neurons related to dopamine. Non-clinical animal models mainly used in Parkinson's disease research include drug-induced models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine, and genetically modified transgenic animal models. Parkinson's diagnosis can be made using brain imaging of the substantia nigra-striatal dopamine system and using a radiotracer that specifically binds to the dopamine transporter. In this study, 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane was used to confirm the image evaluation cutoff between normal and parkinson's disease models, and to confirm model persistence over time. In addition, the efficacy of single or combined administration of clinically used therapeutic drugs in parkinson's animal models was evaluated. Image analysis was performed using the PMOD software. Converted to standardized uptake value, and analyzed by standardized uptake value ratio by dividing the average value of left striatum by the average value of right striatum obtained by applying positron emission tomography images to the atlas magnetic resonance template. The image cutoff of the normal and the parkinson's disease model was calculated as SUVR=0.829, and it was confirmed that it was maintained during the test period. In the three-drug combination administration group, the right and left striatum showed a high symmetry of more than 0.942 on average and recovered significantly. Images using 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane are thought to be able to diagnose and evaluate treatment efficacy of non-clinical Parkinson's disease.