New chelators for diagnostic and therapeutic pairs of radioactive metal isotopes
用于诊断和治疗放射性金属同位素对的新型螯合剂
基本信息
- 批准号:2740489
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:英国
- 项目类别:Studentship
- 财政年份:2022
- 资助国家:英国
- 起止时间:2022 至 无数据
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
2. Aim of the PhD Project (max 50 words, as bullet points): This project aims to: Develop new chelators that can complex large radioactive metal ions that are used for for PET, SPECT and radiotherapy; Identify the most promising chelator that can bind a diagnostic/therapeutic pair of radioactive metal ions with high stability; Attach the most promising chelator to biological targets (antibodies, peptides) for radiolabelling; Evaluate the in vitro and in vivo biology of radiometal-labelled bioconjugate derivatives of the most promising chelator. Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT), allow quantitative whole-body molecular imaging of cancer. One class of PET and SPECT molecular radiopharmaceuticals incorporates a radioactive metal bound via a chelator attached to a peptide or protein, which targets cell-surface receptors of diseased cells. Systemic Peptide Receptor Radionuclide Therapy (PRRT) of cancer incorporates b-- or a-emitting radiometals into the same molecular architectures to deliver targeted therapeutic radiation. Gallium-68 (68Ga) PET agents and lutetium-177 (177Lu) b--emitting PRRTs have recently made a huge impact in prostate and neuroendocrine cancer in clinics where they are available. The 68Ga and 177Lu agents are used as a diagnostic/therapeutic pair of radiopharmaceuticals, and are often referred to as "theranostic" agents. In this project, the student will prepare new hydrid chelators that combine aza-crown ethers (known to encapsulate lanthanide and actinide metal ions5), with hydroxypyridinones and hydroxypyridinthiones, and explore the coordination chemistry and radiolabelling of these new chelators with a range of metal ions with medically useful radioisotopes, including radioisotopes of Pb2+, Bi3+ and Ac3+ and Th4+ (with a view to assessing applicability with a-emitting isotopes) and imaging radioisotopes such as 89Zr4+, 111In3+ and 201Tl+/3+. The student will then select the most promising chelator, for bioconjugation to a peptide or antibody, as we have done with prior novel chelator derivatives.2,6 The student will radiolabel this bioconjugate with selected imaging and therapeutic radiometals, and undertake in vitro and in vivo experiments to evaluate the biological behaviour of these novel, targeted radiotracers.
2. PhD项目的目的(最多50字,作为要点):该项目旨在:开发新的螯合剂,可以络合用于PET,SPECT和放射治疗的大放射性金属离子;确定最有前途的螯合剂,可以结合诊断/治疗对放射性金属离子,具有高稳定性;将最有前途的螯合剂连接到生物靶点(抗体、肽)用于放射性标记;评价最有前途的螯合剂的放射性标记生物缀合物衍生物的体外和体内生物学。正电子发射断层扫描(PET)和单光子发射计算机断层扫描(SPECT)允许癌症的定量全身分子成像。一类PET和SPECT分子放射性药物通过螯合剂结合到肽或蛋白质上,靶向病变细胞的细胞表面受体。癌症的全身性肽受体放射性核素治疗(PRRT)将发射B-或a-的放射性金属结合到相同的分子结构中以递送靶向治疗辐射。镓-68(68 Ga)PET试剂和镥-177(177 Lu)B-发射PRRT最近在可获得它们的诊所中对前列腺癌和神经内分泌癌产生了巨大影响。68 Ga和177 Lu试剂被用作放射性药物的诊断/治疗对,并且通常被称为“治疗诊断”试剂。在这个专题中,学生将准备新的螯合剂,它将联合收割机氮杂冠醚(已知包封镧系元素和锕系元素金属离子5)与羟基吡啶酮和羟基吡啶硫酮,并探索这些新螯合剂与一系列金属离子的配位化学和放射性标记,所述金属离子具有医学上有用的放射性同位素,包括Pb 2+的放射性同位素,Bi 3+和Ac 3+和Th 4+(为了评估α-发射同位素的适用性)和成像放射性同位素如89 Zr 4+、111 In 3+和201 Tl +/3+。然后,学生将选择最有前途的螯合剂,用于与肽或抗体的生物缀合,就像我们对先前的新型螯合剂衍生物所做的那样。2,6学生将用选定的成像和治疗放射性金属放射性标记这种生物缀合物,并进行体外和体内实验,以评估这些新型靶向放射性示踪剂的生物学行为。
项目成果
期刊论文数量(0)
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其他文献
吉治仁志 他: "トランスジェニックマウスによるTIMP-1の線維化促進機序"最新医学. 55. 1781-1787 (2000)
Hitoshi Yoshiji 等:“转基因小鼠中 TIMP-1 的促纤维化机制”现代医学 55. 1781-1787 (2000)。
- DOI:
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LiDAR Implementations for Autonomous Vehicle Applications
- DOI:
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2021 - 期刊:
- 影响因子:0
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吉治仁志 他: "イラスト医学&サイエンスシリーズ血管の分子医学"羊土社(渋谷正史編). 125 (2000)
Hitoshi Yoshiji 等人:“血管医学与科学系列分子医学图解”Yodosha(涉谷正志编辑)125(2000)。
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Effect of manidipine hydrochloride,a calcium antagonist,on isoproterenol-induced left ventricular hypertrophy: "Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,K.,Teragaki,M.,Iwao,H.and Yoshikawa,J." Jpn Circ J. 62(1). 47-52 (1998)
钙拮抗剂盐酸马尼地平对异丙肾上腺素引起的左心室肥厚的影响:“Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,
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