• 대한방사성의약품학회지
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• 제6권1호
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• pp.3-9
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• 2020

Tetraiodothyroacetic acid (tetrac) is a derivative of thyroid hormone T₄ and causes anti-angiogenesis by blocking T₄ binding to integrin α_vβ₃. In this study, we synthesized [^99mTc]Tc-Cys-Asp-Gly(CDG)-tetrac and evaluated it in vitro as a tumor angiogenesis imaging ligand. The CDG was conjugated to tetrac as a chelator for technetium-99m labeling. The cold vial containing CDG-tetrac, sodium glucoheptonate, and reducing agent was completed under nitrogen-filled atmospheric glove bag. [^99mTc]Tc-CDG-tetrac was synthesized in quantitative yield by heating the cold vial with [^99mTc]TcO₄^- at 100℃ for 30 min. In vitro serum stability of [^99mTc]Tc-CDG-tetrac was measured by incubating the radioligand in 50% fetal bovine serum at 37℃ and analyzing the incubation mixture by radio-TLC, which showed high stability over 6 h (≥ 98%). Cell binding study was carried out by incubating [^99mTc]Tc-CDG-tetrac with human umbilical vein endothelial (HUVE) cells at 37℃ for 6 h. The cell binding of the radioligand increased from 100% at 0.5 h to 293.7% at 6 h in a time-dependent manner. For blocking study, the cells were incubated with the radioligand in the presence of either tetrac (20 μM) or cRGDyK (20 μM) at 37℃ for 4 h. The results demonstrated that the cell binding of the radioligand was inhibited by tetrac (19.1%) or cRGDyK (35.6%), indicating specific binding of the radioligand to integrin α_vβ₃. Thus, this study suggests that [^99mTc]Tc-CDG-tetrac may be a potential radioligand for tumor angiogenesis imaging.

• Bulletin of the Korean Chemical Society
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• 제34권11호
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• pp.3243-3248
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• 2013

The tissue inhibitor of metalloproteinase-2 (TIMP-2) inhibits matrix metalloproteinases activity and modulates cellular proliferation and apoptosis. The human serum albumin-TIMP-2 with folic acid conjugate (termed HT2-folate) was synthesized to promote uptake through folate receptors (FRs), and a corresponding radio-labeled compound was prepared for tumor diagnosis by positron emission tomography (PET). $^{68}Ga$-NOTA-HT2-folate was synthesized from $^{68}Ga$ and the NOTA chelator with HT2-folate. The fusion protein was identified using MALDI-TOF mass spectrometry. The radioligand was prepared with a high radiochemical yield. Cell-surface association of $^{68}Ga$-NOTA-HT2-folate significantly increased over time in FR-positive tumor cells. In animal PET and biodistribution studies, tumor uptake was very high as early as 1 h after radioligand injection. Folate conjugation enhanced the selective receptor-targeting efficacy of HT2 in FRexpressing tumors, and its radioligand will be useful as an in vitro tool and for in vivo tumor diagnosis by PET imaging.

• 대한약리학회지
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• 제27권2호
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• pp.119-123
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• 1991

${\beta}-$수용체 효능약물 ((-)-NE), 길항약물 $((\pm)-propranolol,\;labetalol)$ 및 PDE 억제약물(imazodan, KR-30045, KR-30075 등)에 대한 ${\beta}-adrenoceptor$ binding 실험을 ${\beta}_1/{\beta}_2$ 비선택적 radioligand인 $(-)-[^3H]-DHA$를 사용하여 실시하였다. Saturation 실험에서 ${\beta}_1$ 및 ${\beta}_2$ 수용체를 모두 갖고 있는 rat 좌심실의 ${\beta}$ 수용체에 대한 $(-)-[^3H]-DHA$의 $K_d$ 값은 $1.5{\pm}0.43\;nM$, $B_{max}$는 $22.0{\pm}0.9\;fmol/mg$ protein이었다. $({\pm})propranolol$, labetalol 및 (-)NE는 단일상으로 $(-)-[^3H]-DHA$의 결합을 억제하였으며 Ki 값은 각각 $17.0{\pm}0.43\;nM$, $57.3{\pm}1.30\;nM$, $1.57{\pm}0.95\;{\mu}M$로 나타났다. 실험에 사용한 모든 PDE 억제약물들은 $(-)-[^3H]-DHA$ 결합을 $10^{-3}\;M$의 고농도에서도 10% 미만으로 억제했다. 실험결과, propraolol, labetalol 및 NE는 ${\beta}_1/{\beta}_2$ 수용체에 대해 비선택적인 약물로 나타났으며, imazodan 및 신합성 PDE 억제약물들은 rat 심근에 있는 ${\beta}-$수용체에 친화성이 거의 없음을 알 수 있었다.

• 대한방사성의약품학회지
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• 제2권2호
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• pp.69-72
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• 2016

Since the translocator protein (TSPO) is involved in neurodegeneration diseases, many scientists' interest has been focused on the development of a ligand targeting TSPO. A novel compound based on pyrazolo[1,5 -a] pyrimidine structure, DPA-714, has been studied and considered as a TSPO ligand with high affinity. In this highlight review, several researches for the novel radioligand for the translocator protein are illustrated.

• 대한핵의학회:학술대회논문집
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• 대한핵의학회 2002년도 제41차 추계학술대회
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• pp.27.2-27.2
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• 2002

• 생물정신의학
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• 제3권2호
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• pp.245-250
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• 1996

본 연구는 알코올사용장애 환자의 혈소판막에 있는 serotonin수용체가 대조군과 비교했을 때 어떤 차이가 있는지 알아보기 위해 시행되었다. $_{125}I-LSD$를 radioligand로 사용하여 포화반응을 해 봄으로서 다음의 결과를 얻었다. 1) 환자군과 대조군간은 $B_{max}$에 있어서만 유의한 차이를 보였다(P<0.0017). 2) Type 1군과 type 2군 사이 역시 $B_{max}$에 있어서만 유의한 차이를 보였다(P<0.0396). 3) 알코올남용군과 알코올의존군 사이의 $B_{max}$와 $K_d$는 모두 유의한 차이가 없었다. 위 결과들은 알코올사용장애의 serotonin 결핍가설을 지지해주며 혈소판의 serotonin 수용체 수의 증가가 알코올사용장애의 trait marker가 될 수 있음을 시사해 준다.

• International Journal of Oral Biology
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• 제35권2호
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• pp.69-74
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• 2010

The mu opioid receptor (MOR) has been regarded as the main site of interaction with analgesics in major clinical use, particularly morphine. The repressor element-1 silencing transcription factor (REST) functions as a transcriptional repressor of neuronal genes in non-neuronal cells. However, it is expressed in certain mature neurons, suggesting that it may have complex and novel roles. In addition, the interactions between MOR and REST and their functions remain unclear. In this study, we examined the effects of morphine on the expression of REST mRNA and protein in human neuroblastoma NMB cells to investigate the roles of REST induced by MOR activation in neuronal cells. To determine the effects of morphine on REST expression, we performed RT-PCR, real-time quantitative RT-PCR, western blot analysis and radioligand binding assays in NMB cells. By RTPCR and real-time quantitative RT-PCR, the expression of REST was found to be unchanged by either the MOR agonist morphine or the MOR specific antagonist CTOP. By western blot, morphine was shown to significantly inhibit the expression of REST, but this suppression was completely blocked by treatment with CTOP. In the radioligand binding assay, the overexpression of REST led to an increased opioid ligand binding activity of endogenous MOR in the NMB cells. These results together suggest that morphine inhibits the expression of REST in human neuroblastoma cells through a post-transcriptional regulatory mechanism mediated through MOR.

• Bulletin of the Korean Chemical Society
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• 제33권11호
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• pp.3671-3675
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• 2012

${\beta}$-Amyloid accumulation in the brain is a pathological hallmark of Alzheimer's disease (AD). Since early detection of ${\beta}$-amyloid may facilitate more successful and timely therapeutic interventions, many investigators have focused on developing AD diagnostic reagents that can penetrate the blood-brain barrier (BBB). Oleanolic acid (OA) is a substance found in a variety of plants that has been reported to prevent the progression of AD in mice. In this study, we synthesized and evaluated a new radioligand in which OA was conjugated to lactoferrin (Lf, an iron-binding glycoprotein that crosses the BBB) for the diagnosis of AD. In an in vitro study in which OA-Lf was incubated with ${\beta}$-amyloid (1-42) aggregates for 24 h, we found that OA-Lf effectively inhibited ${\beta}$-amyloid aggregation and fibril formation. In vivo studies demonstrated that $^{123}I$-OA-Lf brain uptake was higher than$^{123}I$-Lf uptake. Therefore, radiolabeled OA-Lf may have diagnostic potential for ${\beta}$-amyloid imaging.

• Bulletin of the Korean Chemical Society
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• 제33권6호
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• pp.1890-1894
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• 2012

Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) have been implicated in the pathogenesis of rheumatoid arthritis, which is angiogenesis dependent. Antibody-based molecular imaging improves targeting, and antibody radiolabeling is useful for monitoring biological events $in$ $vivo$ $via$ PET or SPECT. We investigated the potential of molecular imaging to diagnose arthritis with VEGFR-2 $in$ $vivo$. The $^{123}I$-VEGFR-2 antibody was prepared by the iodogen tube method. The radioligand was injected into arthritic mice, and micro SPECT/CT was performed. The arthritic mice were examined by 4.7-T MRI and immunohistochemistry. The $^{123}I$-VEGFR-2 antibody showed high uptake in the arthritic region at 1 h postinjection on SPECT/CT but no uptake in the control animals after radioligand injection. In MR images, the arthritic tissue of the mice was correlated with regions labeled by the $^{123}I$-VEGFR-2 antibody. Immunohistochemical localization showed markedly increased expression of VEGFR-2 in the endothelial cells, fibroblasts, and macrophages of the arthritic mice.

• 대한핵의학회지
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• 제34권3호
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• pp.159-168
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• 2000

In the 1980s, techniques to image the human subjects in a three-dimensional direction were developed. Two major techniques are SPECT (Single Photon Emission Computed Tomography) and PET (Positron Emission Tomography) which allow the detector to detect a single photon or annihilation photons emitted from the subjects injected with radiopharmaceuticals. Since the latter two techniques can measure the density of receptors, enzymes and transporters in living human, it may be very important project to develop selective methods of labeling with radionuclides and to develop new radiopharmaceuticals. There has been a considerable interest in developing new compounds which specifically bind to dopamine and serotonin receptor and transporters, and it will be thus very useful to label those compounds with radionuclides in order to gain a better understanding in biochemical and pharmacological interactions in living human. This review mentions the characteristics of radioligands for the imaging of dopamine and serotonin receptors and transporters. Although significant progress has been achieved in the development of new PET and SPECT ligands for in vivo imaging of those receptors and transporters, there are continuous needs of new diagnostic radioligands.