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Synthesis and Preclinical Evaluation of Kit-Type 99mTc-Labeled N-(2-Aminoethyl)-3-(4-(2-hydroxy-3-(isopropylaminopropoxy)phenyl)propanamide for SPECT Imaging of Cardiac β1-Adrenoceptor : 심장 β1-아드레날린 수용체 단일광자방출전산화단층촬영 영상을 위한 테크네슘-99m 표지 N-(2-Aminoethyl)-3-(4-(2-hydroxy-3-(isopropylaminopropoxy)phenyl)propanamide의 합성 및 전임상평가
DC Field | Value | Language |
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dc.contributor.advisor | 김상은 | - |
dc.contributor.author | 육영청 | - |
dc.date.accessioned | 2017-07-19T10:57:47Z | - |
dc.date.available | 2017-07-19T10:57:47Z | - |
dc.date.issued | 2017-02 | - |
dc.identifier.other | 000000140732 | - |
dc.identifier.uri | https://hdl.handle.net/10371/133224 | - |
dc.description | 학위논문 (석사)-- 서울대학교 대학원 : 융합과학부, 2017. 2. 김상은. | - |
dc.description.abstract | Technetium-99m is the most widely used radionuclide for SPECT (single-photon emission computed tomography) imaging nowadays because of its ideal nuclear properties (t1/2 = 6 h, 141 keV), simple production, low cost and extensive functional group tolerance. β1-Adrenoreceptor is inextricably bound up with cardiac nervous system and usually have selective reduction in failing human heart. In this work, a novel 99mTc-labeled radiotracer for specific β1-adrenoreceptor binding was prepared and its preclinical evaluation was carried out by serial SPECT images in normal rats.
In order to develop radiotracers for β1-adrenoreceptor, 99mTc-labeled N-(2-aminoethyl)-3-(4-(2-hydroxy-3-(isopropylaminopro- poxy)phenyl)propanamide ([99mTc]1) was synthesized by kit-type formulation. To optimize the labeling condition, a variety of attempts were investigated with different stabilizers including mannitol, NaCl and cyclodextrin. Using mannitol as stabilizer, the precursor was reacted with 99mTcO4- in presence of SnF2 (reducing agent) and ascorbic acid (anti-oxidant) at room temperature for 30 sec, to give [99mTc]1 in excellent radiochemical yield (>95%) and with high radiochemical purity (>98%). Mass Spectrometric and NMR data of the cold authentic compound, rhenium coordinated N-(2-aminoethyl)-3-(4-(2-hydroxy-3-(isopropylaminopropoxy)phenyl)propanamide ([185/187Re]1), were used for the speculation of the structure of [99mTc]1 based on the similar chemical properties between 99mTc and 185/187Re complexes. In serial SPECT images, [99mTc]1 showed high accumulation in the heart and kidneys, while radio-uptake was relatively low in the liver and lung. In vivo inhibition study with excess esmolol (18 mg/kg) or atenolol (2 mg/kg) resulted in remarkable reduced radio-uptake in the heart by 92% and 76%, respectively. This study describes synthesis of precursor (4) and the cold authentic compound ([185/187Re]1), radio-synthesis and in vivo imaging study of [99mTc]1 to evaluate the expression of β1-adrenoceptor in the heart. Our results demonstrated that [99mTc]1 exhibits specific β1-adrenoreceptor binding and potential in vivo bio-kinetic characteristics which make it a promising SPECT radiotracer for assessment of β1-adrenoreceptor in heart diseases. | - |
dc.description.tableofcontents | 1. Introduction 1
1.1 Technetium-99m 1 1.2 β1-Adrenoreceptor and cardiac images 5 1.3 Current radiotracers for β1-adrenoreceptor 10 2. Experimental Section 14 2.1 Synthesis of precursor and [185/187Re]1 14 2.2 Synthesis of [99mTc]1 21 2.3 SPECT/CT imaging study of [99mTc]1 24 2.4 Blocking study 27 3. Results and Discussion 28 3.1 Radio-labeling conditions of [99mTc]1 28 3.2 SPECT/CT images of [99mTc]1 33 3.3 Blocking study with Esmolol or Atenolol 36 4. Conclusion 39 Reference 40 초록 (국문) 47 | - |
dc.format | application/pdf | - |
dc.format.extent | 1543528 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | 99mTc-N-(2-Aminoethyl)-3-(4-(2-hydroxy-3-(isopropyl-aminopropoxy)phenyl)propanamide | - |
dc.subject | cardiac β1-adrenoreceptor | - |
dc.subject | SPECT imaging | - |
dc.subject.ddc | 620 | - |
dc.title | Synthesis and Preclinical Evaluation of Kit-Type 99mTc-Labeled N-(2-Aminoethyl)-3-(4-(2-hydroxy-3-(isopropylaminopropoxy)phenyl)propanamide for SPECT Imaging of Cardiac β1-Adrenoceptor | - |
dc.title.alternative | 심장 β1-아드레날린 수용체 단일광자방출전산화단층촬영 영상을 위한 테크네슘-99m 표지 N-(2-Aminoethyl)-3-(4-(2-hydroxy-3-(isopropylaminopropoxy)phenyl)propanamide의 합성 및 전임상평가 | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | Yingqing Lu | - |
dc.description.degree | Master | - |
dc.citation.pages | 57 | - |
dc.contributor.affiliation | 융합과학기술대학원 융합과학부 | - |
dc.date.awarded | 2017-02 | - |
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