• Nuclear Engineering and Technology
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• 제34권2호
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• pp.146-153
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• 2002

To radiolabel bioactive molecules, we synthesized $^{99m}$Tc-tricarbonyl precursor, [$^{99m}$Tc(CO)$_3$($H_2O$)$_3$]$^{+}$ with a low oxidation state ( I ). The [$^{99m}$Tc(CO)$_3$($H_2O$)$_3$]$^{+}$ was prepared by low pressure carbonylation (1 atm of CO) of [$^{99m}$Tc $O_4$)]$^{[-10]}$ in the presence of NaB $H_4$ resulting in higher than 98% of labeling yield and stability up to 8 hrs. We evaluated the characteristics of $^{99m}$Tc- tricarbonyl labeled bioactive molecules by carrying out in vitro and in vitro study. Prepared [$^{99m}$Tc(CO)$_3$($H_2O$)$_3$]$^{+}$ was then reacted with some ligands of significance in modem diagnostic nuclear medicine and some amino acids. Labeling yields were checked by HPLC and found to be usually high, excluding $^{99m}$Tc-tricarbonyl-MDP, -EDTMP and -mIBG. And the biodistribution properties of $^{99m}$Tc-tricarbonyl complexes applied in rabbit showed different appearance comparing with that of the $^{99m}$Tc-labeling by conventional means. From these results, we conclude that [$^{99m}$Tc(CO)$_3$($H_2O$)$_3$]$^{+}$ is a potential precursor for development of radiopharmaceuticals, especially for labeling of biomolecules.

• Toxicological Research
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• 제29권1호
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• pp.21-25
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• 2013

The selective targeting of an integrin ${\alpha}_v{\beta}_3$ receptor using radioligands may enable the assessment of angiogenesis and integrin ${\alpha}_v{\beta}_3$ receptor status in tumors. The aim of this research was to label a peptidomimetic integrin ${\alpha}_v{\beta}_3$ antagonist (PIA) with $^{99m}Tc(CO)_3$ and to test its receptor targeting properties in nude mice bearing receptor-positive tumors. PIA was reacted with tris-succinimidyl aminotriacetate (TSAT) (20 mM) as a PIA per TSAT. The product, PIA-aminodiacetic acid (ADA), was radiolabeled with $[^{99m}Tc(CO)_3(H_2O)_3]^{+1}$, and purified sequentially on a Sep-Pak C-18 cartridge followed by a Sep-Pak QMA anion exchange cartridge. Using gradient C-18 reverse-phase HPLC, the radiochemical purity of $^{99m}Tc(CO)_3$-ADA-PIA (retention time, 10.5 min) was confirmed to be > 95%. Biodistribution analysis was performed in nude mice (n = 5 per time point) bearing receptor-positive M21 human melanoma xenografts. The mice were administered $^{99m}Tc(CO)_3$-ADA-PIA intravenously. The animals were euthanized at 0.33, 1, and 2 hr after injection for the biodistribution study. A separate group of mice were also co-injected with 200 ${\mu}g$ of PIA and euthanized at 1 hr to quantify tumor uptake. $^{99m}Tc(CO)_3$-ADA-PIA was stable in phosphate buffer for 21 hr, but at 3 and 6 hr, 7.9 and 11.5% of the radioactivity was lost as histidine, respectively. In tumor bearing mice, $^{99m}Tc(CO)_3$-ADA-PIA accumulated rapidly in a receptor-positive tumor with a peak uptake at 20 min, and rapid clearance from blood occurring primarily through the hepatobiliary system. At 20 min, the tumor-to-blood ratio was 1.8. At 1 hr, the tumor uptake was 0.47% injected dose (ID)/g, but decreased to 0.12% ID/g when co-injected with an excess amount of PIA, indicating that accumulation was receptor mediated. These results demonstrate successful $^{99m}TC$ labeling of a peptidomimetic integrin antagonist that accumulated in a tumor via receptor-specific binding. However, tumor uptake was very low because of low blood concentrations that likely resulted from rapid uptake of the agent into the hepatobiliary system. This study suggests that for $^{99m}Tc(CO)_3$-ADA-PIA to be useful as a tumor detection agent, it will be necessary to improve receptor binding affinity and increase the hydrophilicity of the product to minimize rapid hepatobiliary uptake.

• Bulletin of the Korean Chemical Society
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• 제27권8호
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• pp.1189-1193
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• 2006

In order to develop radiopharmaceuticals for targeting a serotonin receptor such as $5-HT_{1A}$, histidine-$C_n$-arylpiperazines (AP) (C = alkyl, n = 2, 3, 4) were prepared in five steps with yields of 25%, 37% and 51%, respectively, and radiolabeled with the $[^{99m}Tc(CO)_3(H_2O)+3]^+$. The $^{99m}Tc(CO)_3$-Histidine-Cn-APs were prepared with a high yield (>99%) and characterized as a tridentate complex with a neutral charge to pass through the blood-brain barrier (BBB). The rhenium complexes with $Re(CO)_3$ were also synthesised and comparative experiments were achieved to evaluate the nature of the $^{99m}Tc$ complexes.

• 대한방사성의약품학회지
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• 제4권2호
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• pp.73-79
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• 2018

In our previous study, tricarbonyl $^{99m}Tc$-labeled TSPO-binding ligand, named $^{99m}Tc$-CB256, having positively charge (+1) was investigated but did not show promising results in in vivo environment despite of a nanomolar binding affinity for TSPO. Because the overall positively charge of $^{99m}Tc$-CB256 would likely interrupt its target protein uptake, we herein designed the neutral tricarbonyl-$^{99m}Tc$ labeled TSPO-binding ligand ($^{99m}Tc$-CB257, 1). $^{99m}Tc$-CB257 was prepared by the facile incorporation of the $[^{99m}Tc(CO)_3]^+$ into a N-(hydroxycarbonylmethyl)-2-picoly moiety in CB257. The radiochemical yield of $^{99m}Tc$-CB257 after HPLC purification was $54.1{\pm}2.4%$ (decay corrected, n = 3). The authentic Re-CB257 (2) was synthesized by using $(NEt_4)_2[Re(CO)_3Br_3]$ in 69.0% yield. The binding affinity of 2 for TSPO was measured in leukocyte and showed approximately 280 times higher than that observed for the positively charged (+1) ligand, Re-CB256 ($K_i=0.57{\pm}0.06nM$ versus $159.3{\pm}8.7nM$, respectively). Our results indicated that 1 can be considered potentially as a new SPECT radiotracer for TSPO-rich cancer and provides the foundation for further in vivo evaluation related with abnormal TSPO-overexpression environments.

• 한국원자력학회:학술대회논문집
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• 한국원자력학회 2001년도 춘계학술발표회요약집
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• pp.548.2-548
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• 2001

• 방사성폐기물학회지
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• 제5권2호
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• pp.133-143
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• 2007

본 연구에서는 다성분의 모의 HLW 용액으로부터 $(TBP-TOA)/NDD-HNO_3$ 혼합추출 계에 의한 Tc, Np, U의 공분리 및 이의 순차 분리 적용 가능성을 평가하였다. 우선 제 3상 방지 및 TBP, TOA,질산 농도 등이 Tc, Np, U의 공분리에 미치는 영향 등을 고려하여 최적 조건으로 (30% TBP-0.5% TOA)/NDD-1M $HNO_3$ 계를 선정하였다. 이때 추출율은 Tc (81%), Np (85%), U (93%), Am/RE 원소 (9% 이하) Pd (약 8%), 기타 원소 (5% 이하)로 Tc, Np 및 U의 공분리는 매우 우수하였으나, 조업 측면에서 Zr의 선 제거 (약 99 % 이상)가 요구되었다. 그리고 공추출된 Tc, Np 및 U을 Tc (역추출제 : 5 M $HNO_3$)${\rightarrow}Np$ 환원 (역추출제 : 0.1 M AHA)${\rightarrow}U$ (역추출제 : 0.01 M $HNO_3$)의 순으로 순차 분리하여 각각의 분리계수를 평가하였으며, 이때 Tc은 95%, Np은 98%, U은 99%를 회수할 수 있었다.

• Bulletin of the Korean Chemical Society
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• 제30권5호
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• pp.1107-1112
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• 2009

The aim of this study is to develop and synthesize $5-HT_{1A}$ receptor imaging agents with WAY-100635 moiety and $^{99m}Tc(CO)_3$ core. WAY-100635 is commonly known as $5-HT_{1A}$ antagonist and its labeled compound ([$^{11}C$] WAY-100635) has been used as effective radioligand for imaging brain $5-HT_{1A}$ receptors with PET(Positron Emission Tomography). However, there are several restrictions in using a radioisotope of C-11 and requires for more effective radioisotopes and ligands. In order to produce a structure most similar to WAY-100635, WAY-100635 derivatives containing a cysteine chelator were designed and confirmed by using in silico (Hyperchem). The novel compounds (7a, 7b, 7c) were prepared in five or 7 steps with yields of 16%, 36% and 42%, respectively and radiolabeled with $[^{99m}Tc(CO)_3(H_2O)_3]^{+}$. The labeling yield was 99% for all the newly synthesized compounds. [$^{99m}Tc(CO)_3$]- WAY-100635 derivatives show a neutral charge which were confirmed by paper electrophoresis.

• Toxicological Research
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• 제28권4호
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• pp.235-240
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• 2012

$^{99m}Tc$ tricarbonyl glycine monomers, trimers, and pentamers were synthesized and evaluated for their radiolabeling and in vivo distribution characteristics. We synthesized a $^{99m}Tc$-tricarbonyl precursor with a low oxidation state (I). $^{99m}Tc(CO)_3(H_2O)_3^+$ was then made to react with monomeric and oligomeric glycine for the development of bifunctional chelating sequences for biomolecules. Labeling yields of $^{99m}Tc$-tricarbonyl glycine monomers and oligomers were checked by high-performance liquid chromatography. The labeling yields of $^{99m}Tc$-tricarbonyl glycine and glycine oligomers were more than 95%. We evaluated the characteristics of $^{99m}Tc$-tricarbonyl glycine oligomers by carrying out a lipophilicity test and an imaging study. The octanol-water partition coefficient of $^{99m}Tc$ tricarbonyl glycine oligomers indicated hydrophilic properties. Single-photon emission computed tomography imaging of $^{99m}Tc$-tricarbonyl glycine oligomers showed rapid renal excretion through the kidneys with a low uptake in the liver, especially of $^{99m}Tc$ tricarbonyl triglycine. Furthermore, we verified that the addition of triglycine to prototype biomolecules (AGRGDS and RRPYIL) results in the improvement of radiolabeling yield. From these results, we conclude that triglycine has good characteristics for use as a bifunctional chelating sequence for a $^{99m}Tc$-tricarbonyl-based biomolecular imaging probe.

• 대한수의학회지
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• 제44권1호
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• pp.15-21
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• 2004

This paper describes the development of $^{99m}Tc$ tricarbonyl cysteine as potential renal function diagnostic radiopharmaceutical and evaluation of its biological characteristics using experimental animals. l-Cysteine was labeled efficiently with $^{99m}Tc$ tricarbonyl precursor $([^{99m}Tc(CO)_3(H_2O)_3)]^{+})$ under 30 min heating at ${75^{\circ}C}$. Labeling yield and stability were analyzed by high performance liquid chromatography (HPLC). The biodistribution property of $^{99m}Tc$ tricarbonyl cysteine in mice and its dynamic imaging profiles in rabbits were carried out. To investigate the excretion mechanism of $^{99m}Tc$ tricarbonyl cysteine, tubular transport inhibition test with probenecid was adopted. $^{99m}Tc$ tricarbonyl cysteine was obtained with a high labeling yield under the moderate condition. The results of biodistribution experiments of $^{99m}Tc$ tricarbonyl cysteine in ICR mice at 3 and 90 min provided that $^{99m}Tc$ tricarbonyl cysteine was very highly accumulated in the kidney and bladder, thereby almost 99% of $^{99m}Tc$ tricarbonyl cysteine was excreted within 90 min post injection. The same results were confirmed by the whole body dynamic images for 30 minutes and static images in rabbits at given time intervals after injection. Renogram of $^{99m}Tc$ tricarbonyl cysteine in rabbits showed that its $T_{max}$ and $T_{1/2}$ of $^{99m}Tc$ tricarbonyl cysteine were $2.33{\pm}0.56$ and $4.30{\pm}0.79$ min, respectively. The $T_{max}$ of $^{99m}Tc$ tricarbonyl cysteine with probenecid pretreatment was $2.30{\pm}0.17$ min, whereas $T_{1/2}$ of that with probenecid pretreatment was $17.0{\pm}32.47$ min. $T_{1/2}$ of $^{99m}Tc$ tricarbonyl cysteine with probenecid pretreatment was significantly different, as compared to the result without probenecid (p<0.0001). The results showed that the excretion of $^{99m}Tc$ tricarbonyl cysteine was extremely affected by probenecid. Therefore, $^{99m}Tc$ tricarbonyl cysteine was rapidly excreted from the kidney principally by the tubular secretion.

• 대한핵의학회지
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• 제30권3호
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• pp.367-371
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• 1996

본 연구에서는 $Bz-MAG_3$를 합성한 후 동결건조 된 키트를 제조하였으며, 이를 $^{99m}Tc$로 표지 후 $^{99m}Tc-MAG_3$의 방사화학적 특성 및 동물체내에서의 분포를 알아보았다. 1) 합성된 $^{99m}Tc-MAG_3$의 $R_f$값은 0.78, 표지효율은 $97.5{\pm}1.9%$ (n=10)로 나타났다. 2) $^{99m}Tc-MAG_3$를 사용하여 얻은 신기능영상은 $^{99m}Tc$-DTPA를 사용한 경우에서 보다 더 선명한 영상을 나타냈다. 3) $^{99m}Tc-MAG_3$를 사용한 ICR-마우스실험(n=10)에서 $T_{max}$(분)는 $^{99m}Tc-MAG_3$ (n=10)에서 1.4-1.5분으로 $^{99m}Tc$-DTPA (n=7)의 2.7분 보다 1.2분 정도 빠른 것을 보였고(P<0.05), $T_{1/2}$는 $^{99m}Tc-MAG_3$(n=10)에서 4.3-4.8분으로 $^{99m}Tc$-DTPA (n=7)의 3.8-4.5분과 비슷한 결과를 보였다. 방광출현 시간은 $^{99m}Tc-MAG_3$와 $^{99m}Tc$-DTPA 모두 2분 이내로 나타났다. 합성한 $Bz-MAG_3$ 키트가 높은 표지효율과 신장의 선명한 동적영상을 나타내는 것으로 보아 시판중인 신장기능 영상용 방사성의약품을 대치하여 사용할 수 있을 것으로 사료된다.