Somatostatin Receptor Based PET Imaging of Gene Transfer

基于生长抑素受体的基因转移 PET 成像

基本信息

  • 批准号:
    7433269
  • 负责人:
  • 金额:
    $ 28.88万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2005
  • 资助国家:
    美国
  • 起止时间:
    2005-06-01 至 2010-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Gene therapy trials would benefit from the ability to determine the location, magnitude, and change in magnitude over time of the expression of delivered genes. Thus far, gene transfer efficiency has been evaluated by obtaining tissue biopsies at predetermined times post treatment. This method of determining gene transfer efficiency is undesirable due to its invasiveness and its inability to generate a global picture of gene transfer, since it is limited to the small piece of tissue(s) examined. Numerous groups have been developing methods for non-invasively imaging gene transfer. We have utilized the human somatostatin receptor subtype 2 (hSSTR2) as a reporter gene along with various radiolabeled somatostatin analogs for gamma ray imaging of gene transfer. However, this system is limited by 1) overexpression of hSSTR2 may have an impact on cell physiology and homeostasis; 2) hSSTR2 is endogenously expressed on certain human tissues; and 3) somatostatin analogs are eliminated through the kidneys which can interfere with signal detection. Therefore, we hypothesize that the hSSTR2 reporter system can be improved through modification of the receptor itself by uncoupling the receptor from G proteins and through the development of novel targeting ligands that recognize a novel epitope inserted into hSSTR2. The first Aim will investigate the ability of somatostatin analogs radiolabeled with positron emitters to quantify different levels of hSSTR2 expression, in vitro and in vivo. The second Aim will construct diabodies and minibodies targeted toward an alternative epitope inserted into hSSTR2 and evaluate these constructs in a manner similar to the somatostatin analogs in Aim 1. These first two Aims are intended to determine the most optimal radiopharmaceutical as a reporter probe for PET imaging. The third Aim will focus on making and evaluating mutants of hSSTR2 that uncouple the receptor from G proteins. The final Aim will use the best mutant hSSTR2 (developed in Aim 3) and the most optimal radiopharmaceutical to determine the activity and efficacy of a therapeutic gene. This is intended to demonstrate that the system can be used to non-invasively detect therapeutic gene transfer through PET imaging. This proposal should result in improvement of the existing hSSTR2 reporter system for imaging gene transfer.
描述(由申请人提供): 基因治疗试验将受益于确定递送基因表达的位置、幅度和幅度随时间的变化的能力。到目前为止,基因转移效率已经通过在治疗后预定时间获得组织活检来评估。这种确定基因转移效率的方法是不希望的,因为它的侵入性和它不能产生基因转移的全局图像,因为它限于所检查的小块组织。许多研究小组一直在开发非侵入性成像基因转移的方法。我们已经利用人生长抑素受体亚型2(hSSTR 2)作为报告基因沿着与各种放射性标记的生长抑素类似物用于基因转移的γ射线成像。然而,该系统受到以下限制:1)hSSTR 2的过表达可能对细胞生理学和体内平衡产生影响; 2)hSSTR 2在某些人体组织上内源性表达;和3)生长抑素类似物通过肾脏消除,这可能干扰信号检测。因此,我们假设hSSTR 2报告系统可以通过受体本身的修饰来改善,通过将受体从G蛋白上解偶联,以及通过开发识别插入hSSTR 2的新表位的新型靶向配体。第一个目标将调查的能力,生长抑素类似物放射性标记的正电子发射体定量不同水平的hSSTR 2的表达,在体外和体内。第二个目标将构建靶向插入hSSTR 2的替代表位的双抗体和微型抗体,并以与目标1中的生长抑素类似物类似的方式评估这些构建体。前两个目标旨在确定最佳放射性药物作为PET成像的报告探针。第三个目标将集中于制造和评估hSSTR 2的突变体,其使受体与G蛋白解偶联。最终的目标将使用最好的突变hSSTR 2(在目标3中开发)和最佳的放射性药物来确定治疗基因的活性和功效。这旨在证明该系统可用于通过PET成像非侵入性检测治疗性基因转移。这一建议应导致现有的hSSTR 2报告系统的成像基因转移的改善。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Adenoviral-mediated imaging of gene transfer using a somatostatin receptor-cytosine deaminase fusion protein.
使用生长抑素受体-胞嘧啶脱氨酶融合蛋白进行腺病毒介导的基因转移成像。
  • DOI:
    10.1038/cgt.2015.14
  • 发表时间:
    2015
  • 期刊:
  • 影响因子:
    6.4
  • 作者:
    Lears,KA;Parry,JJ;Andrews,R;Nguyen,K;Wadas,TJ;Rogers,BE
  • 通讯作者:
    Rogers,BE
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Buck E. Rogers其他文献

789: Integrin antagonism to mitigate radiation-induced pulmonary fibrosis: iDISCO-based 3-D SHG imaging
789:整联蛋白拮抗以减轻辐射诱导的肺纤维化:基于IDISCO的3-D SHG成像
  • DOI:
    10.1016/s0167-8140(24)01324-0
  • 发表时间:
    2024-05-01
  • 期刊:
  • 影响因子:
    5.300
  • 作者:
    William C Y Lo;Peter G. Ruminiski;Amanda Klaas;Felicia Grogan;Lori Strong;Julie K. Schwarz;Clifford G. Robinison;Buck E. Rogers;Carmen Bergom
  • 通讯作者:
    Carmen Bergom
#27. First-in-human evaluation of safety and dosimetry of <sup>64</sup>Cu-LLP2A for PET imaging
  • DOI:
    10.1016/j.jbo.2024.100565
  • 发表时间:
    2024-04-01
  • 期刊:
  • 影响因子:
  • 作者:
    Richard Laforest;Anchal Ghai;Tyler J. Fraum;Reiko Oyama;Jennifer Frye;Helen Kaemmerer;Greg Gaehle;Tom Voller;Cedric Mpoy;Buck E. Rogers;Mark Fiala;Kooresh I. Shoghi;Samuel Achilefu;Michael Rettig;Ravi Vij;John F. DiPersio;Sally Schwarz;Monica Shokeen;Farrokh Dehdashti
  • 通讯作者:
    Farrokh Dehdashti
Using Integrin αsubv/subβsub6/sub-Targeted Positron Emission Tomography Imaging to Longitudinally Monitor Radiation-Induced Pulmonary Fibrosis In Vivo
利用整合素αvβ6靶向正电子发射断层成像术在体内纵向监测放射性肺纤维化
  • DOI:
    10.1016/j.ijrobp.2024.08.034
  • 发表时间:
    2025-02-01
  • 期刊:
  • 影响因子:
    6.500
  • 作者:
    William C.Y. Lo;Cristian W. Villas Boas;Truc T. Huynh;Amanda Klaas;Felicia Grogan;Lori Strong;Pamela Samson;Clifford G. Robinson;Buck E. Rogers;Carmen Bergom
  • 通讯作者:
    Carmen Bergom

Buck E. Rogers的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Buck E. Rogers', 18)}}的其他基金

Small Molecule GPCR Ligands for Oncologic Imaging
用于肿瘤成像的小分子 GPCR 配体
  • 批准号:
    9977505
  • 财政年份:
    2020
  • 资助金额:
    $ 28.88万
  • 项目类别:
The PET Radiotracer Translation and Resource Center (PET-RTRC) Training & Dissemination
PET 放射性示踪剂翻译和资源中心 (PET-RTRC) 培训
  • 批准号:
    10715917
  • 财政年份:
    2018
  • 资助金额:
    $ 28.88万
  • 项目类别:
SYNTHESIS OF CATIONIC STEROID COMPOUNDS FOR DETECTION OF BACTERIAL INFECTIONS
用于检测细菌感染的阳离子类固醇化合物的合成
  • 批准号:
    9090097
  • 财政年份:
    2015
  • 资助金额:
    $ 28.88万
  • 项目类别:
DEVELOPMENT OF A MICRORT SYSTEM
MICRORT系统的开发
  • 批准号:
    7826778
  • 财政年份:
    2009
  • 资助金额:
    $ 28.88万
  • 项目类别:
DEVELOPMENT OF PET RADIOPHARMACEUTICALS TARGETING GRPR
针对 GRPR 的 PET 放射性药物的开发
  • 批准号:
    7731138
  • 财政年份:
    2009
  • 资助金额:
    $ 28.88万
  • 项目类别:
DEVELOPMENT OF PET RADIOPHARMACEUTICALS TARGETING GRPR
针对 GRPR 的 PET 放射性药物的开发
  • 批准号:
    8077958
  • 财政年份:
    2009
  • 资助金额:
    $ 28.88万
  • 项目类别:
DEVELOPMENT OF PET RADIOPHARMACEUTICALS TARGETING GRPR
针对 GRPR 的 PET 放射性药物的开发
  • 批准号:
    8266454
  • 财政年份:
    2009
  • 资助金额:
    $ 28.88万
  • 项目类别:
Somatostatin Receptor Based PET Imaging of Gene Transfer
基于生长抑素受体的基因转移 PET 成像
  • 批准号:
    7015559
  • 财政年份:
    2005
  • 资助金额:
    $ 28.88万
  • 项目类别:
Somatostatin Receptor Based PET Imaging of Gene Transfer
基于生长抑素受体的基因转移 PET 成像
  • 批准号:
    6856960
  • 财政年份:
    2005
  • 资助金额:
    $ 28.88万
  • 项目类别:
Somatostatin Receptor Based PET Imaging of Gene Transfer
基于生长抑素受体的基因转移 PET 成像
  • 批准号:
    7227724
  • 财政年份:
    2005
  • 资助金额:
    $ 28.88万
  • 项目类别:

相似海外基金

Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
  • 批准号:
    495434
  • 财政年份:
    2023
  • 资助金额:
    $ 28.88万
  • 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
  • 批准号:
    10586596
  • 财政年份:
    2023
  • 资助金额:
    $ 28.88万
  • 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
  • 批准号:
    10590479
  • 财政年份:
    2023
  • 资助金额:
    $ 28.88万
  • 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
  • 批准号:
    10642519
  • 财政年份:
    2023
  • 资助金额:
    $ 28.88万
  • 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
  • 批准号:
    23K06011
  • 财政年份:
    2023
  • 资助金额:
    $ 28.88万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
  • 批准号:
    10682117
  • 财政年份:
    2023
  • 资助金额:
    $ 28.88万
  • 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
  • 批准号:
    10708517
  • 财政年份:
    2023
  • 资助金额:
    $ 28.88万
  • 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
  • 批准号:
    10575566
  • 财政年份:
    2023
  • 资助金额:
    $ 28.88万
  • 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
  • 批准号:
    23K15696
  • 财政年份:
    2023
  • 资助金额:
    $ 28.88万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
  • 批准号:
    23K15867
  • 财政年份:
    2023
  • 资助金额:
    $ 28.88万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了