• Korean Journal of Radiology
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• v.24 no.7
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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.

• The Korean Journal of Nuclear Medicine
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• v.33 no.3
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• pp.298-305
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• 1999

Purpose: N-(3-[$^{18}F$]Fluoropropyl)-$2{\beta}$-carbomethoxy-$3{\beta}$-(4-iodophenyl)nortropane [$^{18}F$]FP-CIT) has been shown to be very useful for imaging the dopamine transporter. However, synthesis of this radiotracer is somewhat troublesome. In this study, we used a new method for the preparation of [$^{18}F$]FP-CIT to increase radiochemical yield and effective specific activity. Materials and Methods: [$^{18}F$]FP-CIT was prepared by N-alkylation of nor-${\beta}$-CIT (2 mg) with 3-bromo-1-[$^{18}F$]fluoropropane in the presence of $Et_3N$ (5-6 drops of $DMF/CH_3CN$, $140^{\circ}C$, 20 min). 3-Bromo-1-[$^{18}F$]fluoropropane was synthesized from $5{\mu}L$ of 3-bromo-1-trifluoromethanesulfonyloxypropane (3-bromopropyl-1-triflate) and $nBu_4N^{18}F$ at $80^{\circ}C$. The final compound was purified by reverse phase HPLC and formulated in 13% ethanol in saline. Results: 3-Bromo-1-[$^{18}F$]fluoropropane was obtained from 3-bromopropyl-1-triflate and $nBu_4N^{18}F$ in 77-80% yield. N-Alkylation of nor-${\beta}$-CIT with 3-bromo-1-[$^{18}F$]fluoropropane was carried out at $140^{\circ}C$ using acetonitrile containing a small volume of DMF as the solvents. The overall yield of [$^{18}F$]FP-CIT was 5-10% (decay-corrected) with a radiochemical purity higher than 99% and effective specific activity higher than the one reported in the literature based on their HPLC data. The final [$^{18}F$]FP-CIT solution had the optimal pH (7.0) and it was pyrogen-free. Conclusion: In this study, 3-bromopropyl-1-triflate was used as the precursor for the [$^{18}F$]fluorination reaction and new conditions were developed for purification of [$^{18}F$]FP-CIT by HPLC. We established this new method for the preparation of [$^{18}F$]FP-CIT, which gave high effective specific activity and relatively good yield.

• Journal of radiological science and technology
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• v.40 no.4
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• pp.595-603
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• 2017

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 optimal 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 $^{18}F$ FP-CIT injected into the phantom's hot sphere and background (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 acquired 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.

• Journal of Korean Neurosurgical Society
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• v.56 no.5
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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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• v.41 no.2
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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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• v.25 no.3
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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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• v.43 no.2
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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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• 1997.05a
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• pp.145-145
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• 1997