• Title/Summary/Keyword: Imaging agent

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Adaptive Image Rescaling for Weakly Contrast-Enhanced Lesions in Dedicated Breast CT: A Phantom Study (약하게 조영증강된 병변의 유방 전용 CT 영상의 대조도 개선을 위한 적응적 영상 재조정 방법: 팬텀 연구)

  • Bitbyeol Kim;Ho Kyung Kim;Jinsung Kim;Yongkan Ki;Ji Hyeon Joo;Hosang Jeon;Dahl Park;Wontaek Kim;Jiho Nam;Dong Hyeon Kim
    • Journal of the Korean Society of Radiology
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    • v.82 no.6
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    • pp.1477-1492
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    • 2021
  • Purpose Dedicated breast CT is an emerging volumetric X-ray imaging modality for diagnosis that does not require any painful breast compression. To improve the detection rate of weakly enhanced lesions, an adaptive image rescaling (AIR) technique was proposed. Materials and Methods Two disks containing five identical holes and five holes of different diameters were scanned using 60/100 kVp to obtain single-energy CT (SECT), dual-energy CT (DECT), and AIR images. A piece of pork was also scanned as a subclinical trial. The image quality was evaluated using image contrast and contrast-to-noise ratio (CNR). The difference of imaging performances was confirmed using student's t test. Results Total mean image contrast of AIR (0.70) reached 74.5% of that of DECT (0.94) and was higher than that of SECT (0.22) by 318.2%. Total mean CNR of AIR (5.08) was 35.5% of that of SECT (14.30) and was higher than that of DECT (2.28) by 222.8%. A similar trend was observed in the subclinical study. Conclusion The results demonstrated superior image contrast of AIR over SECT, and its higher overall image quality compared to DECT with half the exposure. Therefore, AIR seems to have the potential to improve the detectability of lesions with dedicated breast CT.

A Study on Preparation of 3'-$[^{18}F]$Fluoro-3'-deoxythymidine and Its Biodistribution in 9L Glioma Bearing Rats (3'-$[^{18}F]$Fluoro-3'-deoxythymidine의 합성과 9L glioma 세포를 이식한 래트에서의 체내동태에 관한 연구)

  • Shim, Ah-Young;Moon, Byung-Seok;Lee, Tae-Sup;Lee, Kyo-Chul;An, Gwang-Il;Yang, Seung-Dae;Yu, Kook-Hyun;Cheon, Gi-Jeong;Choi, Chang-Woon;Lim, Sang-Moo;Chun, Kwon-Soo
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.5
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    • pp.263-270
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    • 2006
  • Purpose: Several radioisotope-labeled thymidine derivatives such as $[^{11}C]$thymidine was developed to demonstrate cell proliferation in tumor. But it is difficult to track metabolism with $[^{11}C]$thymidine due to rapid in vivo degradation and its short physical half-life. 3'-$[^{18}F]$fluoro-3'-deoxythymidine ($[^{18}F]$FLT) was reported to have the longer half life of fluorine-18 and the lack of metabolic degradation in vivo. Here, we described the synthesis of the 3'-$[^{18}F]$fluoro-3'-deoxythymidine ($[^{18}F]$FLT) and compared with $([^{18}F]FET)\;and\;([^{18}F]FDG)$ in cultured 9L cell and obtained the biodistribution and PET image in 9L tumor hearing rats. Material and Methods: For the synthesis of $[^{18}F]$FLT, 3-N-tert-butoxycarbonyl-(5'-O-(4,4'-dimet hoxytriphenylmethyl)-2'-deoxy-3'-O-(4-nitrobenzenesulfonyl)-${\beta}$-D-threopentofuranosyl)thymine was used as a FLT precursor, on which the tert-butyloxycarbonyl group was introduced to protect N3-position and nitrobenzenesulfonyl group. Radiolabeling of nosyl substitued precursor with $^{18}F$ was performed in acetonitrile at $120^{\circ}C$ and deproteced with 0.5 N HCI. The cell uptake was measured in cultured 9L glioma cell. The biodistribution was evaluated in 9L tumor bearing rats after intravenous injection at 10 min, 30 min, 60 min and 120 min and obtained PET image 60 minutes after injection. Results: The radiochemical yield was about 20-30% and radiochemical purity was more than 95% after HPLC purification. Cellular uptake of $[^{18}F]$FLT was increased as time elapsed. At 120 min post-injection, the ratios of tumor/blood, tumor/muscle and tumor/brain were $1.61{\pm}0.34,\;1.70{\pm}0.30\;and\;9.33{\pm}2.22$, respectively. The 9L tumor was well visualized at 60 min post injection in PET image. Conclusion: The uptake of $[^{18}F]$FLT in tumor was higher than in normal brain and PET image of $[^{18}F]$FLT was acceptable. These results suggest the possibility of $[^{18}F]$FLT at an imaging agent for brain tumor.

Quantitative Analysis of GBCA Reaction by Mol Concentration Change on MRI Sequence (MRI sequence에 따른 GBCA 몰농도별 반응에 대한 정량적 분석)

  • Jeong, Hyun Keun;Jeong, Hyun Do;Kim, Ho Chul
    • Journal of the Institute of Electronics and Information Engineers
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    • v.52 no.2
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    • pp.182-192
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    • 2015
  • In this paper, we introduce how to change the reaction rate as mol concentration when we scan enhanced MRI with GBCA(Gadolinium Based Contrast Agent), Also show the changing patterns depending on diverse MRI sequences which are made by different physical principle. For this study, we made MRI phantom ourselves. We mixed 500 mmol Gadoteridol with Saline in each 28 different containers from 500 to 0 mmol. After that, MR phantom was scanned by physically different MRI sequences which are T1 SE, T2 FLAIR, T1 FLAIR, 3D FLASH, T1 3D SPACE and 3D SPCIR in 1.5T bore. The results were as follows : *T1 Spin echo's Total SI(Signal Intensity) was 15608.7, Max peak was 1352.6 in 1 mmol. *T2 FLAIR's Total SI was 9106.4, Max peak was 0.4 1721.6 in 1 mmol. *T1 FLAIR's Total SI was 20972.5, Max peak was 1604.9 in 1 mmol. *3D FLASH's Total SI was 20924.0, Max peak was 1425.7 in 40 mmol. *3D SPACE 1mm's Total SI was 6399.0, Max peak was 528.3 in 3 mmol. *3D SPACE 5mm's Total SI was 6276.5, Max peak was 514.6 in 2 mmol. *3D SPCIR's Total SI was 1778.8, Max peak was 383.8 in 0.4 mmol. In most sequences, High signal intensity was shown in diluted lower concentration rather than high concentration, And also graph's max peak and pattern had difference value according to the each different sequence. Through this paper which have quantitative result of GBCA's reaction rate depending on sequence, We expect that practical enhanced MR protocol can be performed in clinical field.

Production of $[^{18}F]F_2$ Gas for Electrophilic Substitution Reaction (친전자성 치환반응을 위한 $[^{18}F]F_2$ Gas의 생산 연구)

  • Moon, Byung-Seok;Kim, Jae-Hong;Lee, Kyo-Chul;An, Gwang-Il;Cheon, Gi-Jeong;Chun, Kwon-Soo
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.4
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    • pp.228-232
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    • 2006
  • Purpose: electrophilic $^{18}F(T_{1/2}=110\;min)$ radionuclide in the form of $[^{18}F]F_2$ gas is of great significance for labeling radiopharmaceuticals for positron omission tomography (PET). However, its production In high yield and with high specific radioactivity is still a challenge to overcome several problems on targetry. The aim of the present study was to develop a method suitable for the routine production of $[^{18}F]F_2$ for the electrophilic substitution reaction. Materials and Methods: The target was designed water-cooled aluminum target chamber system with a conical bore shape. Production of the elemental fluorine was carried out via the $^{18}O(p,n)^{18}F$ reaction using a two-step irradiation protocol. In the first irradiation, the target filled with highly enriched $^{18}O_2$ was irradiated with protons for $^{18}F$ production, which were adsorbed on the inner surface of target body. In the second irradiation, the mixed gas ($1%[^{19}F]F_2/Ar$) was leaded into the target chamber, fellowing a short irradiation of proton for isotopic exchange between the carrier-fluorine and the radiofluorine absorbed in the target chamber. Optimization of production was performed as the function of irradiation time, the beam current and $^{18}O_2$ loading pressure. Results: Production runs was performed under the following optimum conditions: The 1st irradiation for the nuclear reaction (15.0 bar of 97% enriched $^{18}O_2$, 13.2 MeV protons, 30 ${\mu}A$, 60-90 min irradiation), the recovery of enriched oxygen via cryogenic pumping; The 2nd irradiation for the recovery of absorbed radiofluorine (12.0 bar of 1% $[^{19}F]fluorine/argon$ gas, 13.2 MeV protons, 30 ${\mu}A$, 20-30 min irradiation) the recovery of $[^{18}F]fluorine$ for synthesis. The yield of $[^{18}F]fluorine$ at EOB (end of bombardment) was achieved around $34{\pm}6.0$ GBq (n>10). Conclusion: The production of $^{18}F$ electrophilic agent via $^{18}O(p,n)^{18}F$ reaction was much under investigation. Especially, an aluminum gas target was very advantageous for routine production of $[^{18}F]fluorine$. These results suggest the possibility to use $[^{18}F]F_2$ gas as a electrophilic substitution agent.

The Effect of Intravenous Contrast on SUV Value in $^{18}F$-FDG PET/CT using Diagnostic High Energy CT (진단용 고선량 CT를 이용한 $^{18}F$-FDG PET/CT 촬영시 정맥 조영제가 SUV 값에 미치는 영향)

  • Jeong, Young-Jin;Kang, Do-Young
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.3
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    • pp.169-176
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    • 2006
  • Purpose: According to the development of CT scanner in PET/CT system, the role of CT unit as a diagnostic tool has been more important. To improve the diagnostic ability of CT scanner, it is a key aspect that CT scanning has to be performed with high dose energy and intravenous (IV) contrast. So we investigated the effect of IV contrast media on the maximum SUV (maxSUV) of normal tissues and pathologic lesions using PET/CT scanner with high dose CT scanning. Materials & Methods: The study enrolled 13 patients who required PET/CT evaluation. At first, the patients were performed whole body non-contrast CT (NCCT-120 kVp, 130 mAs) scan. Then contrast enhanced CT (CECT) scan was performed immediately. Finally PET scan was followed. The PET omission data were reconstructed twice, once with the NCCT and again with the CECT. We measured the maxSUV of 10 different body regions that were considered as normal in ail patients. Also pathologic lesions were investigated. Results: There were not seen focal artifacts in PET images based on CT with IV contrast agent. Firstly, 130 normal regions in 13 patients were evaluated. The maxSUV was significantly different between two PET images (p<0.00)). The maxSUV was $1.1{\pm}0.5$ in PET images with CECT-corrected attenuation and $1.0{\pm}0.5$ in PET images with NCCI-corrected attenuation. The limit of agreement was $0.1{\pm}0.3$ in Bland-Altman analysis. Especially there were significant differences in 6 of 10 regions, apex and base of the right lung, ascending aorta, segment 6 & segment 8 of the liver and spleen (p<0.05). Secondly, 39 pathologic lesions were evaluated. The maxSUV was significantly different between two PET images (p<0.001). The maxSUV was $4.7{\pm}2.0$ in PET images with CECT-corrected attenuation and $4.4{\pm}2.0$ in PET images with NCCT-corrected attenuation. The limit of agreement was $0.4{\pm}0.8$ in Bland-Altman analysis. Conclusion: Although there were increases of maxSUVs in the PET images based on CT with IV contrast agent, it was very narrow in the range of limit of agreement. So there was no significant effect to clinical interpretation for PET images that were corrected attenuation with high dose CT using IV contrast.

Radiolabeling of NOTA and DOTA with Positron Emitting $^{68}$Ga and Investigation of In Vitro Properties (양전자 방출핵종 $^{68}$Ga을 이용한 NOTA와 DOTA의 표지 및 시험관내 특성 연구)

  • Jeong, Jae-Min;Kim, Young-Ju;Lee, Yun-Sang;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.4
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    • pp.330-336
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    • 2009
  • Purpose: We established radiolabeling conditions of NOTA and DOTA with a generator-produced PET radionuclide $^{68}$Ga and studied in vitro characteristics such as stability, serum protein binding, octanol/water distribution, and interference with other metal ions. Materials and Methods: Various concentrations of NOTA 3HCl and DOTA 4HCl were labeled with 1 mL $^{68}$GaCl$_3$ (0.18$\sim$5.75 mCi in 0.1 M HCl in various pH. NOTA 3HCl (0.373 mM) was labeled with $^{68}$GaCl$_3$(0.183$\sim$0.232 mCi/0.1 M HCl 1.0 mL) in the presence of CuCl$_2$, FeCl$_2$, InCl$_3$, FeCl$_3$, GaCl$_3$, MgCl$_2$ or CaCl$_2$ (0$\sim$6.07 mM) at room temperature. The labeling efficiencies of $^{68}$Ga-NOTA and $^{68}$Ga-DOTA were checked by ITLC-SG using acetone or saline as mobile phase. Stabilities, protein bindings, and octanol distribution coefficients of the labeled compounds also were investigated. Results: $^{68}$Ga-NOTA and $^{68}$Ga-DOTA were labeled optimally at pH 6.5 and pH 3.5, respectively, and the chelates were stable for 4 hr either in the reaction mixture at room temperature or in the human serum at 37$^{\circ}C$. NOTA was labeled at room temperature while DOTA required heating for labeling. $^{68}$Ga-NOTA labeling efficiency was reduced by CuCl$_2$, FeCl$_2$, InCl$_2$, FeCl$_3$ or CaCl$_3$, however, was not influenced by MgCl$_2$ or CaCl$_2$. The protein binding was low (2.04$\sim$3.32%). Log P value of $^{68}$Ga-NOTA was -3.07 indicating high hydrophilicity. Conclusion: We found that NOTA is a better bifunctional chelating agent than DOTA for $^{68}$Ga labeling. Although, $^{68}$Ga-NOTA labeling is interfered by various metal ions, it shows high stability and low serum protein binding.

The Magnetic Relaxation Properties of DTPA-bis(4-carboxycyclohexyl) amide Paramagnetic Gd-chelates (DTPA-bis(4-carboxycyclohexyl)amide 상자성 복합체의 자기이완특성에 관한 연구)

  • Kim, In-Sung;Lee, Young-Ju;Lee, Jae-Jun;Kim, Ju-Hyun;Kim, Yoo-Kyung;Sujit, Dutta;Kim, Suk-Kyung;Kim, Tae-Jeong;Kang, Duk-Sik;Chang, Yong-Min
    • Investigative Magnetic Resonance Imaging
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    • v.10 no.1
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    • pp.20-25
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    • 2006
  • Purpose : To evaluate the NMR relaxation properties of newly developed high performance paramagnetic complexes. Materials and methods : 4-aminomethylcyclohexane carboxylic acid (0.63g, 4 mmol) was mixed with the suspension solution of DMF (15mL) and DTPA-bis-anhydride (0.71g, 2 mmol) to synthesize the ligand. The ligand was then mixed with Gd2O3 (0.18g, 0.5 mmol) to synthesize Gd-chelate. For the measurement of magnetic relaxivity of paramagnetic compounds, the compounds were diluted to 1mM and then the relaxation times were measured at 1.5T(64 MHz). Inversion-recovery pulse sequence was employed for T1 relaxation measurement and CPMG(Carr-Purcell-Meiboon-Gill) pulse sequence was employed for T2 relaxation measurement. Using MATLAB(Version 7.1) program, T1 magnetic relaxation map, R1 map, T2 magnetic relaxation map and R2 map were developed to represent magnetic relaxation time and magnetic relaxivity as image. Results : Compared to $R1=4.9mM^{-1}sec^{-1}$ and $R2=4.8mM^{-1}sec^{-1}$ of Omniscan (Gadodiamide), which is commercially available paramagnetic MR agent, R1 of SUK090(Gd-C32H74N5O24) was $12.46mM^{-1}sec^{-1}$ and R1 of SUK091(Gd-C34H78N5O24) was $12.77mM^{-1}sec^{-1}$. However, R1 of SUK092(Gd-C30H56N5O17) was decreased to $2.09mM^{-1}sec^{-1}$. In case of R2, SUK090(Gd-C32H74N5O24) was $8.76mM^{-1}sec^{-1}$ and SUK091(Gd-C34H78N5O24) was $7.60mM^{-}1sec^{-1}$ whereas SUK092(Gd-C30H56N5O17) was decreased to $1.82mM^{-1}sec^{-1}$. Conclusion : Among three new paramagnetic complexes, SUK090(Gd-C32H74N5O24) and SUK091(Gd-C34H78N5O24) showed higher T1, T2 magnetic relaxation rates than that of commercially available paramagnetic MR agent and thus expected to have more contrast enhancement effect.

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Radiosynthesis of $[^{11}C]6-OH-BTA-1$ in Different Media and Confirmation of Reaction By-products. ($[^{11}C]6-OH-BTA-1$ 조제 시 생성되는 부산물 규명과 반응용매에 따른 표지 효율 비교)

  • Lee, Hak-Jeong;Jeong, Jae-Min;Lee, Yun-Sang;Kim, Hyung-Woo;Lee, Eun-Kyoung;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul
    • Nuclear Medicine and Molecular Imaging
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    • v.41 no.3
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    • pp.241-246
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    • 2007
  • Purpose: $[^{11}C]6-OH-BTA-1$ ([N-methyl-$^{11}C$]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole, 1), a -amyloid imaging agent for the diagnosis of Alzheimer's disease in PET, can be labeled with higher yield by a simple loop method. During the synthesis of $[^{11}C]1$, we found the formation of by-products in various solvents, e.g., methylethylketone (MEK), cyclohexanone (CHO), diethylketone (DEK), and dimethylformamide (DMF). Materials and Methods: In Automated radiosynthesis module, 1 mg of 4-aminophenyl-6-hydroxybenzothiazole (4) in 100 l of each solvent was reacted with $[^{11}C]methyl$ triflate in HPLC loop at room temperature (RT). The reaction mixture was separated by semi-preparative HPLC. Aliquots eluted at 14.4, 16.3 and 17.6 min were collected and analyzed by analytical HPLC and LC/MS spectrometer. Results: The labeling efficiencies of $[^{11}C]1$ were $86.0{\pm}5.5%$, $59.7{\pm}2.4%$, $29.9{\pm}1.8%$, and $7.6{\pm}0.5%$ in MEK, CHO, DEK and DMF, respectively. The LC/MS spectra of three products eluted at 14.4, 16.3 and 17.6 mins showed m/z peaks at 257.3 (M+1), 257.3 (M+1) and 271.3 (M+1), respectively, indicating their structures as 1, 2-(4'-aminophenyl)-6-methoxybenzothiazole (2) and by-product (3), respectively. Ratios of labeling efficiencies for the three products $([^{11}C]1:[^{11}C]2:[^{11}C]3)$ were $86.0{\pm}5.5%:5.0{\pm}3.4%:1.5{\pm}1.3%$ in MEK, $59.7{\pm}2.4%:4.7{\pm}3.2%:1.3{\pm}0.5%$ in CHO, $9.9{\pm}1.8%:2.0{\pm}0.7%:0.3{\pm}0.1%$ in DEK and $7.6{\pm}0.5%:0.0%:0.0%$ in DMF, respectively. Conclusion: The labeling efficiency of $[^{11}C]1$ was the highest when MEK was used as a reaction solvent. As results of mass spectrometry, 1 and 2 were conformed. 3 was presumed.

Synthesis of a Dopamine Transporter Imaging Agent, N-(3-[$^{18}F$]fluoropropyl)-$2{\beta}$-carbomethoxy-$3{\beta}$-(4-iodophenyl)nortropane (도파민운반체 방사성추적자 N-(3-[$^{18}F$Fluoropropyl)-$2{\beta}$-carbomethoxy-$3{\beta}$-(4-iodophenyl)nortropane의 합성)

  • Choe, Yearn-Seong;Oh, Seung-Jun;Chi, Dae-Yoon;Kim, Sang-Eun;Choi, Yong;Lee, Kyung-Han;Kim, Byung-Tae
    • 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.

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$^{17}O$ NMR Study On Water Excharge Rate of Paramagnetic Contrast Agents ($^{17}O$ NMR 기법을 이용한 상자성 자기공명조영제의 물분자 교환에 관한 연구)

  • Yongmin Chang;Sung Wook Hong;Moon Jung Hwang;Il Soo Rhee;Duk-Sik Kang
    • Investigative Magnetic Resonance Imaging
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    • v.5 no.1
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    • pp.33-37
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    • 2001
  • Purpose : The water exchange rate between bulk water and bound water is an important parameter in deciding the efficiency of paramagnetic contrast agents. In this study, we evaluated the water exchange rates of various Gd-chelates using oxygen-17 NMR technique. Material and Methods : The samples (Gd-DTPA, Gd-DTPA-BMA, Gd-DOTA, Gd-EOB-DTPA) were prepared by mixing 5% $^{17}O-enriched$ water (Isotech, USA). The pH of the samples was adjusted to physiological value [pH=7.0] by buffer solution. The variable temperature $^{17}O-NMR$ measurements were performed using Bruker-600 (14.1 T, 81.3 MHz) spectrometer. Bruker VT-1000 temperature control units were used to stabilize the temperature. The $^{17}O$ spin-spin relaxation times (T2) were measured using Carr-Purcell-Meiboom-Gill (CPMG)I pulse sequence with 24 echo trains. The variable temperature T2 relaxation data were then fitted into Solomon-Bloembergen equations using least square fit algorithm to estimate the water exchange times. Results : From the measured $^{17}O-NMR$ relaxation rates, the determined water exchange rates at 300K are $0.42{\;}{\mu}s$ for Gd-DTPA, $1.99{\;}{\mu}s$ for Gd-DTPA-BMA, $0.27{\;}{\mu}s$ for Gd-DOTA, and $0.11{\;}{\mu}s$ for Gd-EOB-DTPA. The Gd-DTPA-BMA showed slowest exchange whereas Gd-EOB-DTPA had fastest water exchange rate. In addition, it was found that the water exchange rates (${\tau}_m$) of all samples had exponential temperature dependence with different decay constant. Conclusion : $^{17}O-NMR$ relaxation rate measurements, when combined with variable temperature technique, provide a solid tool for studying water exchange rate, which is very important in investigating the detailed mechanism of relaxation enhancement effect of the paramagnetic contrast agents.

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