Small Molecule GPCR Ligands for Oncologic Imaging
用于肿瘤成像的小分子 GPCR 配体
基本信息
- 批准号:9977505
- 负责人:
- 金额:$ 19.68万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-05-01 至 2022-02-28
- 项目状态:已结题
- 来源:
- 关键词:AffinityAnimalsBindingBiodistributionBiological ModelsBombesinBombesin ReceptorBreast Cancer CellCell Surface ReceptorsCellsDetectionDevelopmentDissociationEmission-Computed TomographyFamilyFutureG-Protein-Coupled ReceptorsGenesGlutamineGoalsHumanImageImmunohistochemistryIn Situ HybridizationIn VitroIndividualKineticsLabelLigandsMalignant NeoplasmsMalignant neoplasm of prostateMammalian CellMessenger RNAMusNeurotensin ReceptorsNormal tissue morphologyPC3 cell linePenetrationPeptide ReceptorPeptidesPermeabilityPhysiological ProcessesPlayPositronPositron-Emission TomographyPropertyPublicationsQuantitative AutoradiographyRadioactiveRadioisotopesRadiolabeledRadionuclide ImagingRadiopharmaceuticalsRoleSerumSomatostatin ReceptorSurveysT47DTissuesTracerTumor TissueVasoactive Intestinal Peptide ReceptorsXenograft procedureanalogbasecancer cellcancer imagingcancer typedesignhuman tissueimaging agentimaging studyin vivoinsightlipophilicitymalignant breast neoplasmmetabolic abnormality assessmentmouse modelneurotransmissionnoveloverexpressionpeptide analogpeptide hormonepiperidinepre-clinicalprostate cancer cellradiochemicalradioligandradiotracerreceptorsmall moleculesubcutaneoussuccesstumortumor xenograftuptake
项目摘要
Abstract
G protein-coupled receptors (GPCRs) are the largest family of cell surface receptor proteins in mammalian
cells. In humans, they are encoded by over 800 individual genes and are widely expressed in human tissues,
where they control a wide range of physiological processes. They play a prominent role in neurotransmission,
but also have been shown to be overexpressed in a variety of cancers. While small organic molecule based
positron-emission tomography (PET) imaging agents have been developed for imaging GPCRs involved in
neurotransmission, GPCRs that are expressed on cancer cells have been targeted with radioactively labeled
hormone peptides. In this regard, somatostatin receptors (SSTRs), gastrin-releasing peptide receptors
(GPCRs), neurotensin receptors (NTSRs), and vasoactive intestinal peptide receptors (VPACs) have been
targeted in a variety of cancer types with different radiolabeled peptides. These peptide based agents have had
some success for both imaging and therapy of tumors (particularly the SSTR peptides), however, the
development of small molecule analogs may have advantages over peptides since they can be suitably designed
to modulate potency, selectivity, lipophilicity, and cell permeability to possibly avoid poor tissue penetration, poor
serum stability, and quick elimination. This would be the first study to evaluate a small molecule PET agent for
imaging GPCRs expressed on tumors. We propose to target GRPR as a model system. In recent years, our
group and others have focused on the development of bombesin (BN) peptide analogs radiolabeled with
positron-emitting radionuclides for positron-emission tomographic (PET) imaging of GRPR-positive tumors in
preclinical mouse models. Some of these peptide analogs have been evaluated in human trials with the most
prominent being 68Ga-RM2. A survey of the existing small molecule compounds which act against GRPR has
identified the antagonist, PD176252, as a potential starting point for developing radiolabeled analogs that bind
to GRPR in the context of prostate and breast cancer. The scientific premise is that these small molecule analogs
will have different properties in terms of cell uptake and dissociation kinetics as compared to peptide tracers and
thus may be superior as imaging agents.
摘要
G蛋白偶联受体是哺乳动物细胞表面最大的受体蛋白家族
细胞。在人类中,它们由800多个单独的基因编码,并在人类组织中广泛表达,
在那里它们控制着广泛的生理过程。它们在神经传递中扮演着重要的角色,
但也已被证明在各种癌症中过度表达。而基于有机小分子的
正电子发射断层扫描(PET)显像剂已被开发用于成像GPCR,涉及
神经传递,表达在癌细胞上的GPCR已经被放射性标记的靶向
荷尔蒙多肽。在这方面,生长抑素受体(SSTRs)、胃泌素释放肽受体
(GPCRs)、神经降压素受体(NTSRs)和血管活性肠肽受体(VPACs)
针对多种癌症类型,使用不同的放射性标记多肽。这些基于多肽的试剂已经有了
然而,在肿瘤的成像和治疗(特别是SSTR肽)方面取得了一些成功,
开发小分子类似物可能比多肽更有优势,因为它们可以被适当地设计
为了调节效力、选择性、亲脂性和细胞渗透性,以可能避免不良的组织渗透
血清稳定,消除快。这将是第一次评估小分子PET试剂的研究
对肿瘤上表达的GPCRs进行成像。我们建议将GRPR作为一个示范系统。近年来,我们的
小组和其他人专注于用放射性标记的蛙皮素(BN)多肽类似物的开发
正电子发射核素在GRPR阳性肿瘤正电子发射断层显像中的应用
临床前小鼠模型。其中一些多肽类似物已经在人体试验中进行了评估,
突出的是68Ga-RM2。一项针对GRPR的现有小分子化合物的研究综述
确定拮抗剂PD176252是开发结合结合的放射性标记类似物的潜在起点
在前列腺癌和乳腺癌的背景下,GRPR。科学前提是这些小分子类似物
在细胞摄取和解离动力学方面将具有不同的性质,与多肽示踪剂和
因此,作为显像剂可能更好。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
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
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:
$ 19.68万 - 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:
$ 19.68万 - 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:
$ 19.68万 - 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:
$ 19.68万 - 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:
$ 19.68万 - 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:
$ 19.68万 - 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:
$ 19.68万 - 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:
$ 19.68万 - 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:
7433269 - 财政年份:2005
- 资助金额:
$ 19.68万 - 项目类别:
相似海外基金
The earliest exploration of land by animals: from trace fossils to numerical analyses
动物对陆地的最早探索:从痕迹化石到数值分析
- 批准号:
EP/Z000920/1 - 财政年份:2025
- 资助金额:
$ 19.68万 - 项目类别:
Fellowship
Animals and geopolitics in South Asian borderlands
南亚边境地区的动物和地缘政治
- 批准号:
FT230100276 - 财政年份:2024
- 资助金额:
$ 19.68万 - 项目类别:
ARC Future Fellowships
The function of the RNA methylome in animals
RNA甲基化组在动物中的功能
- 批准号:
MR/X024261/1 - 财政年份:2024
- 资助金额:
$ 19.68万 - 项目类别:
Fellowship
Ecological and phylogenomic insights into infectious diseases in animals
对动物传染病的生态学和系统发育学见解
- 批准号:
DE240100388 - 财政年份:2024
- 资助金额:
$ 19.68万 - 项目类别:
Discovery Early Career Researcher Award
RUI:OSIB:The effects of high disease risk on uninfected animals
RUI:OSIB:高疾病风险对未感染动物的影响
- 批准号:
2232190 - 财政年份:2023
- 资助金额:
$ 19.68万 - 项目类别:
Continuing Grant
RUI: Unilateral Lasing in Underwater Animals
RUI:水下动物的单侧激光攻击
- 批准号:
2337595 - 财政年份:2023
- 资助金额:
$ 19.68万 - 项目类别:
Continuing Grant
A method for identifying taxonomy of plants and animals in metagenomic samples
一种识别宏基因组样本中植物和动物分类的方法
- 批准号:
23K17514 - 财政年份:2023
- 资助金额:
$ 19.68万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
Analysis of thermoregulatory mechanisms by the CNS using model animals of female-dominant infectious hypothermia
使用雌性传染性低体温模型动物分析中枢神经系统的体温调节机制
- 批准号:
23KK0126 - 财政年份:2023
- 资助金额:
$ 19.68万 - 项目类别:
Fund for the Promotion of Joint International Research (International Collaborative Research)
Using novel modelling approaches to investigate the evolution of symmetry in early animals.
使用新颖的建模方法来研究早期动物的对称性进化。
- 批准号:
2842926 - 财政年份:2023
- 资助金额:
$ 19.68万 - 项目类别:
Studentship
Study of human late fetal lung tissue and 3D in vitro organoids to replace and reduce animals in lung developmental research
研究人类晚期胎儿肺组织和 3D 体外类器官在肺发育研究中替代和减少动物
- 批准号:
NC/X001644/1 - 财政年份:2023
- 资助金额:
$ 19.68万 - 项目类别:
Training Grant