• Korean Journal of Radiology
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• 제24권7호
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• pp.690-697
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• 2023

Objective: ¹⁸F-FP-CIT positron emission tomography (PET) is known for its high sensitivity and specificity for evaluating striatal dopamine transporter (DAT) binding. Recently, for the early diagnose of Parkinson's disease, many researchers focused on the diagnosis of synucleinopathy in organs involved in non-motor symptoms of Parkinson's disease. We investigated the feasibility of salivary gland uptake on ¹⁸F-FP-CIT PET as a new biomarker in patients with parkinsonism. Materials and Methods: A total of 219 participants with confirmed or presumed parkinsonism, including 54 clinically diagnosed idiopathic Parkinson's disease (IPD), 59 suspected and yet undiagnosed, and 106 with secondary parkinsonism, were enrolled. The standardized uptake value ratio (SUVR) of the salivary glands was measured on both early and delayed ¹⁸F-FP-CIT PET scans using the cerebellum as the reference region. Additionally, the delayed-to-early ratio (DE_ratio) of salivary gland was obtained. The results were compared between patients with different PET patterns. Results: The SUVR in early ¹⁸F-FP-CIT PET scan was significantly higher in patients with IPD pattern compared that in the non-dopaminergic degradation group (0.5 ± 0.19 vs. 0.6 ± 0.21, P < 0.001). Compared with the non-dopaminergic degradation group, the DE_ratio was significantly lower in patients with IPD (5.05 ± 1.7 vs. 4.0 ± 1.31, P < 0.001) or atypical parkinsonism patterns (5.05 ± 1.7 vs. 3.76 ± 0.96, P < 0.05). The DE_ratio was moderately and positively correlated with striatal DAT availability in both the whole striatum (r = 0.37, P < 0.001) and posterior putamen (r = 0.36, P < 0.001). Conclusion: Parkinsonism patients with an IPD pattern exhibited a significant increase in uptake on early ¹⁸F-FP-CIT PET and a decrease in the DE_ratio in the salivary gland. Our findings suggest that salivary gland uptake of dual-phase ¹⁸F-FP-CIT PET can provide diagnostic information on DAT availability in patients with Parkinson's disease.

• 대한핵의학회지
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• 제33권3호
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• pp.298-305
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• 1999

목적: PET을 이용하여 도파민운반체를 영상화하는데 유용한 [$^{18}F$]FP-CIT는 그 동안 여러 연구팀들에 의하여 합성이 시도되어졌으나 합성의 난이성 때문에 문제가 되어왔다. 이 연구에서는 새로운 방법에 의하여 유효비방사능이 높은 [$^{18}F$]FP-CIT를 높은 수율로 합성하고자 하였다. 대상 및 방법: [$^{18}F$]Fluoropropyl기를 도입하기 위하여 사용된 3-bromo-1-[$^{18}F$]Fluoropropane은 THF 용매 하에서 3-bromo-propyl-1-triflate $5{\mu}L$와 $nBu_4N^{18}F$를 $80^{\circ}C$에서 2분 동안 가열하여 얻어졌으며 정제하지 않고 직접 알킬화반응에 사용하였다. 이렇게 생성된 3-bromo-1-[$^{18}F$]fluoropropane에 nor-${\beta}$-CIT를 넣고 DMF $5{\sim}6$방울이 함유된 아세토니트릴을 반응용매, $Et_3N$을 생성된 산의 중화제로 사용하여 140f에서 20분동안가열하였다. 생성된 [$^{18}F$]FP-CIT는 HPLC에 의해 정제되고 13% 에탄올이 함유된 생리식염수를 사용하여 제제화하였다. 정도관리는 HPLC 및 방사능 박층크로마토그라피에 의한 분석, pH, 발열성 검사로 이루어졌다. 결과· 3-Bromo-1-[$^{18}F$]Fluoropropane은 3-bromopropyl-1-triflate의 triflate기를 $^{18}F$으로 치환하여 $77{\sim}80%$의 높은 방사화학적 수율로 얻어졌으며 같은 반응용기에 nor-${\beta}$-CIT를 넣고 $140^{\circ}C$의 반응온도에서 아세토니트릴과 최소량의 DMF를 사용하여 알킬화반응을 실행하였다. 이때 DMF의 높은 극성과 비점 때문에 HPLC로 정제할 때 문제가 되었으므로 초기에 0.8% $Et_3N$을 포함한 물만을 사용하는 정제방법을 개발하였다. [$^{18}F$]FP-CIT의 동정은 비방사성 동일물질인 FP-CIT와 동시에 HPLC에 주입하여 확인되었다. [$^{18}F$]FP-CIT의 정도관리를 실행한 결과, 방사화학적 순도는 99% 이상, 유효비방사능은 $37GBq/{\mu}mol$ 이상으로 우수하였으며 총 감쇠보정된 방사화학적 수율도 $5{\sim}10%$로 높았다. 최종생성물의 pH는 약 7.0이었으며 발열물질은 없었다. 결론: 이 연구에서는 [$^{18}F$]fluorination 반응의 전구물질로서 3-bromopropyl-1-triflate를 사용하였고 HPLC 정제 조건을 새롭게 개발함으로써 유효비방사능이 높고 비교적 수율도 높은 [$^{18}F$]FP-CIT를 합성하는 새로운 방법을 확립하였다. 이 [$^{18}F$]FP-CIT는 뇌 도파민운반체의 체내 연구에 유용하게 사용될 것으로 사료된다.

• 대한방사선기술학회지:방사선기술과학
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• 제40권4호
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• pp.595-603
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• 2017

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 (radi oacti vi ty rati o 3:1)에 $^{18}F$ FP-CIT를 주입하고, 관전압(100, 120 kVp)과 관전류(80, 140, 200 mAs)의 조건을 변화시키며 CT 스캔을 실험하였다(기준조건; 120 kVp, 140 mAs). 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 가능할 것으로 사료된다.

• Journal of Korean Neurosurgical Society
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• 제56권5호
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• pp.383-389
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• 2014

Objective : Neural tissue transplantation has been a promising strategy for the treatment of Parkinson's disease (PD). However, transplantation has the disadvantages of low-cell survival and/or development of dyskinesia. Transplantation of cell aggregates has the potential to overcome these problems, because the cells can extend their axons into the host brain and establish synaptic connections with host neurons. In this present study, aggregates of human brain-derived neural stem cells (HB-NSC) were transplanted into a PD animal model and compared to previous report on transplantation of single-cell suspensions. Methods : Rats received an injection of 6-OHDA into the right medial forebrain bundle to generate the PD model and followed by injections of PBS only, or HB-NSC aggregates in PBS into the ipsilateral striatum. Behavioral tests, multitracer (2-deoxy-2-[$^{18}F$]-fluoro-D-glucose ([$^{18}F$]-FDG) and [$^{18}F$]-N-(3-fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl)nortropane ([$^{18}F$]-FP-CIT) microPET scans, as well as immunohistochemical (IHC) and immunofluorescent (IF) staining were conducted to evaluate the results. Results : The stepping test showed significant improvement of contralateral forelimb control in the HB-NSC group from 6-10 weeks compared to the control group (p<0.05). [$^{18}F$]-FP-CIT microPET at 10 weeks posttransplantation demonstrated a significant increase in uptake in the HB-NSC group compared to pretransplantation (p<0.05). In IHC and IF staining, tyrosine hydroxylase and human ${\beta}2$ microglobulin (a human cell marker) positive cells were visualized at the transplant site. Conclusion : These results suggest that the HB-NSC aggregates can survive in the striatum and exert therapeutic effects in a PD model by secreting dopamine.

• Nuclear Medicine and Molecular Imaging
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• 제41권2호
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• pp.118-131
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• 2007

Neurotransmitter imaging with radiopharmaceuticals plays major role for understanding of neurological and psychiatric disorders such as Parkinson's disease and depression. Radiopharmaceuticals for neurotransmitter imaging can be divided to dopamine transporter imaging radiopharmaceuticals and serotonin trnasporter imaging radiopharmaceuticals. Many kinds of new dopamine transporter imaging radiopharmcaeuticals has a tropane ring and they showed different biological properties according to the substituted functional group on tropane ring. After the first clinical trials with $[^{123}I]{\beta}-CIT$, alkyl chain substituent introduced to tropane ring amine to decrease time for imaging acquisition and to increase selectivity. From these results, $[^{123}I]PE2I$, [18F]FE-CNT, $[^{123}I]FP-CIT$ and $[^{18}F]FP-CIT$ were developed and they showed high uptake on the dopamine transporter rich regions and fast peak uptake equilibrium time within 4 hours after injection. $[^{11}C]McN$ 5652 was developed for serotonin trnasporter imaging but this compound showed slow kinetics and high background radioactivity. To overcome these problems, new diarylsulfide backbone derivatives such as ADAM, ODAM, AFM, and DASB were developed. In these candidates, $[^{11}C]AFM$ and $[^{11}C]DASB$ showed high binding affinity to serotonin transporter and fast in vivo kinetics. This paper gives an overview of current status on dopamine and serotonin transporter imaging radiopharmaceuitcals and the development of new lead compounds as potential radiopharmaceuticals by medicinal chemistry.

• Korean Journal of Radiology
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• 제25권3호
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• pp.267-276
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• 2024

Objective: To evaluate the diagnostic performance of susceptibility map-weighted imaging (SMwI) taken in different acquisition planes for discriminating patients with neurodegenerative parkinsonism from those without. Materials and Methods: This retrospective, observational, single-institution study enrolled consecutive patients who visited movement disorder clinics and underwent brain MRI and ¹⁸F-FP-CIT PET between September 2021 and December 2021. SMwI images were acquired in both the oblique (perpendicular to the midbrain) and the anterior commissure-posterior commissure (AC-PC) planes. Hyperintensity in the substantia nigra was determined by two neuroradiologists. ¹⁸F-FP-CIT PET was used as the reference standard. Inter-rater agreement was assessed using Cohen;s kappa coefficient. The diagnostic performance of SMwI in the two planes was analyzed separately for the right and left substantia nigra. Multivariable logistic regression analysis with generalized estimating equations was applied to compare the diagnostic performance of the two planes. Results: In total, 194 patients were included, of whom 105 and 103 had positive results on ¹⁸F-FP-CIT PET in the left and right substantia nigra, respectively. Good inter-rater agreement in the oblique (κ = 0.772/0.658 for left/right) and AC-PC planes (0.730/0.741 for left/right) was confirmed. The pooled sensitivities for two readers were 86.4% (178/206, left) and 83.3% (175/210, right) in the oblique plane and 87.4% (180/206, left) and 87.6% (184/210, right) in the AC-PC plane. The pooled specificities for two readers were 83.5% (152/182, left) and 82.0% (146/178, right) in the oblique plane, and 83.5% (152/182, left) and 86.0% (153/178, right) in the AC-PC plane. There were no significant differences in the diagnostic performance between the two planes (P > 0.05). Conclusion: There are no significant difference in the diagnostic performance of SMwI performed in the oblique and AC-PC plane in discriminating patients with parkinsonism from those without. This finding affirms that each institution may choose the imaging plane for SMwI according to their clinical settings.

• Nuclear Medicine and Molecular Imaging
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• 제43권2호
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• pp.91-99
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• 2009

Noninvasive imaging of molecular and biological processes in living subjects with positron emission tomography(PET) provides exciting opportunities to monitor metabolism and detect diseases in humans. Measuring these processes with PET requires the preparation of specific molecular imaging probes labeled with $^{18}F$-fluorine. In this review we describe recent methods and novel trends for the introduction of $^{18}F$-fluorine into molecules which in turn are intended to serve as imaging agents for PET study. Nucleophilic $^{18}F$-fluorination of some halo- and mesyloxyalkanes to the corresponding $^{18}F$-fluoroalkanes with $^{18}F$-fluoride obtained from an $^{18}O(p,n)^{18}F$ reaction, using novel reaction media system such as an ionic liquidor tert-alcohol, has been studied as a new method for $^{18}F$-fluorine labeling. Ionic liquid method is rapid and particularly convenient because $^{18}F$-fluoride in $H_2O$ can be added directly to the reaction media, obviating the careful drying that is typically required for currently used radiofluorination methods. The nonpolar protic tert-alcohol enhances the nucleophilicity of the fluoride ion dramatically in the absence of any kind of catalyst, greatly increasing the rate of the nucleophilic fluorination and reducing formation of byproducts compared with conventional methods using dipolar aprotic solvents. The great efficacy of this method is a particular advantage in labeling radiopharmaceuticals with $^{18}F$-fluorine for PETimaging, and it is illustrated by the synthesis of $^{18}F$-fluoride radiolabeled molecular imaging probes, such as $^{18}F$-FDG, $^{18}F$-FLT, $^{18}F$-FP-CIT, and $^{18}F$-FMISO, in high yield and purity and in shorter times compared to conventional syntheses.

• 대한핵의학회:학술대회논문집
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• 대한핵의학회 1997년도 제36차 춘계학술대회 초록집
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• pp.145-145
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• 1997