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Development of 68Ga-Labeled Multivalent Nitroimidazole Derivatives for Hypoxia Imaging : 저산소 영상을 위한 68Ga-표지 다가(多價) 나이트로이미다졸 유도체 개발
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | Jae Min Jeong | - |
| dc.contributor.author | SEELAM SUDHAKARA REDDY | - |
| dc.date.accessioned | 2017-07-14T01:17:42Z | - |
| dc.date.available | 2017-07-14T01:17:42Z | - |
| dc.date.issued | 2016-08 | - |
| dc.identifier.other | 000000136243 | - |
| dc.identifier.uri | https://hdl.handle.net/10371/121809 | - |
| dc.description | 학위논문 (박사)-- 서울대학교 대학원 : 방사선응용생명과학전공, 2016. 8. 정재민. | - |
| dc.description.abstract | Abstract
Development of 68Ga-Labeled Multivalent Nitroimidazole Derivatives for Hypoxia Imaging Seelam Sudhakara Reddy Department of Nuclear Medicine Interdisciplinary Program in Radiation Applied Life Science The Graduate School Seoul National University College of Medicine Radiolabeled nitroimidazole (NI) derivatives have been extensively studied for imaging hypoxia. To increase the hypoxic tissue uptake, we developed 68Ga-labeled agents based on mono-, bis-, and trisnitroimidazole conjugates with the chelating agent 1,4,7-triazacyclononane-1,4,7-tris[methyl(2-carboxyethyl)phosphinic acid] (TRAP). All the three agents showed high radiolabeling yields (>96%) and were found to be stable up to 4 h in prepared medium at room temperature and in human serum at 37 °C. The trivalent agent showed a significant increase in hypoxic to normoxic uptake ratio (p < 0.005) according to the in vitro cell uptake experiments. Immunohistochemical analysis confirmed the presence of hypoxia in xenografted CT26 tumor tissue. The trivalent derivative (68Ga-3: 0.17 ± 0.04, 68Ga-4: 0.33 ± 0.04, 68Ga-5: 0.45 ± 0.09, and 68Ga-6: 0.47 ± 0.05% ID/g) showed the highest uptake by tumor cells according to the biodistribution studies in CT-26 xenografted mice. All the nitroimidazole derivatives showed significantly higher uptake by tumor cells than the control agent (p < 0.05) at 1 h post-injection. The trivalent derivative (68Ga-3: 0.10 ± 0.06 | - |
| dc.description.abstract | 68Ga-4: 0.20 ± 0.06 | - |
| dc.description.abstract | 68Ga-5: 0.33 ± 0.08 | - |
| dc.description.abstract | 68Ga-6: 0.59 ± 0.09) also showed the highest standard uptake value for tumor cells at 1 h post-injection in animal PET studies using CT-26 xenografted mice. In conclusion, we successfully synthesized multivalent 68Ga-labeled NI derivatives for imaging hypoxia. Among them, the trivalent agent showed the highest tumor uptake in biodistribution and animal PET studies.
Keywords: trisnitroimidazole | - |
| dc.description.abstract | bisnitroimidazole | - |
| dc.description.abstract | multidentate | - |
| dc.description.abstract | gallium-68 | - |
| dc.description.abstract | hypoxia | - |
| dc.description.abstract | PET.
Student number: 2010-31372 | - |
| dc.description.tableofcontents | 1. Introduction 1
2. Materials and Methods 18 2-1. General 18 2-2. Chemical Synthesis 19 2-3. Radiolabeling 22 2-4. Stability study 23 2-5. Measurement of partition coefficients 23 2-6. Measurement of serum protein binding 24 2-7. In vitro cell uptake study 24 2-8. Immunohistochemical analysis 25 2-9. Biodistribution study of xenografted mice 27 2-10. PET of tumor bearing Mice 27 2-11. Data analysis 28 3. Results and discussion 29 3-1. Synthesis 29 3-2. Radiochemistry 30 3-3. In vitro cell uptake study 35 3-4. Immunohistochemical analysis 38 3-5. Biodistribution in xenografted mice 40 3-6. PET imaging of tumor bearing mice 43 4. Conclusion 47 5. References 48 Appendix 60 Spectral data 1H NMR Spectra 61 13C NMR Spectra 64 31P NMR Spectra 67 Mass Spectra 70 Abstract in Korean 76 | - |
| dc.format | application/pdf | - |
| dc.format.extent | 2618410 bytes | - |
| dc.format.medium | application/pdf | - |
| dc.language.iso | en | - |
| dc.publisher | 서울대학교 대학원 | - |
| dc.subject | trisnitroimidazole | - |
| dc.subject | bisnitroimidazole | - |
| dc.subject | multidentate | - |
| dc.subject | gallium-68 | - |
| dc.subject | hypoxia | - |
| dc.subject | PET. | - |
| dc.subject.ddc | 616 | - |
| dc.title | Development of 68Ga-Labeled Multivalent Nitroimidazole Derivatives for Hypoxia Imaging | - |
| dc.title.alternative | 저산소 영상을 위한 68Ga-표지 다가(多價) 나이트로이미다졸 유도체 개발 | - |
| dc.type | Thesis | - |
| dc.description.degree | Doctor | - |
| dc.citation.pages | 76 | - |
| dc.contributor.affiliation | 의과대학 협동과정 방사선응용생명과학전공 | - |
| dc.date.awarded | 2016-08 | - |
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