Molecular Imaging and Theranostics of Cancer
癌症的分子成像和治疗诊断学
基本信息
- 批准号:10455724
- 负责人:
- 金额:$ 96.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-04 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AchievementAddressAffectAreaAwardBiodistributionBiological MarkersBrainCachexiaCancer DetectionCell membraneClinicalCytotoxic T-LymphocytesDevelopmentDextransEnsureFDA approvedFibroblastsFocal Adhesion Kinase 1Functional ImagingGlycolatesGranulocyte-Macrophage Colony-Stimulating FactorHealthcareHeartHumanImageImmuneImmune checkpoint inhibitorImmunocompetentImmunosuppressionInfiltrationInfrastructureIntercellular FluidLiverMalignant NeoplasmsMetabolicMorbidity - disease rateMusMuscleNear-infrared optical imagingNeoplasm MetastasisOncologistOrganPancreatic Ductal AdenocarcinomaPathologistPathway interactionsPatientsPlayPositron-Emission TomographyResearchRoleSurgeonSymptomsSyndromeTechnologyTranslational ResearchTumor-infiltrating immune cellsXenograft Modelantibody conjugatebasebiomaterial compatibilitycancer cachexiacancer cellcancer therapyeffector T cellimaging probeimproved outcomeinhibitormechanotransductionmolecular imagingmultimodalitynanoparticlenear infrared dyeneoplastic cellpersonalized medicinephotoimmunotherapypre-clinicalradiologistresponsesiRNA deliverytheranosticstriple-negative invasive breast carcinomatumortumor microenvironmenttumor xenograft
项目摘要
Achieving cancer cure, or even control, continues to be a major unanswered challenge in health care despite
the remarkable technological advances of the 21st century. Advances in multi-modal noninvasive molecular
and functional imaging are providing unique opportunities to expand our understanding of cancer, an
understanding that is critical to developing effective and cancer specific treatments. In this resubmission I
have chosen three interactive focus areas within the tumor microenvironment (TME), the tumor
macroenvironment (TMacE), and Theranostics, that will be pursued in triple negative breast cancer (TNBC)
and pancreatic ductal adenocarcinoma (PDAC) human tumor xenografts and syngeneic tumors in immune
competent mice. In the TME focus, we will use imaging to expand our understanding of the focal adhesion
kinase (FAK) mechanotransduction pathway in the metastatic cascade that will include developing PET
imaging probes to detect FAK noninvasively. FAK also plays a role in tumor immune suppression. In the
TMacE focus we will expand our efforts in understanding PDAC induced cachexia that results in a wide range
of symptoms affecting the function of organs such as muscle, liver, brain, and heart, causing significant
morbidity. The tumor secretome holds the key to this syndrome by influencing the `macroenvironment'. We
will focus on characterizing the tumor interstitial fluid (TIF) in preclinical PDAC xenograft models to develop
biomarkers of cachexia and identify potential metabolic targets that will be pursued through the Theranostic
focus. In the Theranostic focus we will direct our efforts and expertise in imaging and NP technology to
improve the outcome of checkpoint inhibitors in TNBC and PDAC. Lack of effector T-cell tumor infiltration has
been identified as a major cause of the poor response to these inhibitors. We will use FDA approved
poly(lactic-co-glycolic acid) PLGA to create cancer cell membrane (CCM) coated `immunosome' NPs
embedded with granulocyte macrophage colony-stimulating factor (GM-CSF) to increase effector T cell tumor
infiltration, and apply molecular imaging to detect the biodistribution of the NPs and the changes in T cell
infiltration. Ultimately we want to use the patients own cancer cells to synthesize the NPs for personalized
medicine. Since FAP-α expressing cancer associated fibroblasts (CAFs) are known to create an immune
suppressive TME, we will use anti-FAP-α antibody conjugated to the near infrared (NIR) dye IR700 to detect
CAFS with NIR imaging and eliminate them selectively in the tumor with PIT. If PIT of FAP-α expressing CAFs
results in increased cytotoxic T cells in tumors, this may have significant applications in combination with
checkpoint inhibitor treatment. We will use siRNA delivery with dextran based biocompatible NPs to
downregulate FAK, and metabolic targets identified in the TMacE focus. I have built a strong network of
collaborators that include clinical oncologists, radiologists, pathologists and surgeons that will ensure the rapid
translation of the research conducted through the R35 award to benefit cancer detection and treatment.
尽管如此,实现癌症治愈,甚至控制,仍然是卫生保健领域一个悬而未决的重大挑战
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)
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Zaver M. Bhujwalla其他文献
Low-dose temozolomide selectively increases glioblastoma’s vascular permeability, tumor microenvironment penetration and the killing potential of systemic actinium-225 α-particle dendrimer-radioconjugates improving treatment efficacy
- DOI:
10.1007/s00259-025-07332-w - 发表时间:
2025-05-14 - 期刊:
- 影响因子:7.600
- 作者:
Rajiv Ranjit Nair;Aira Sarkar;Pooja Hariharan;Kathleen L. Gabrielson;Tony Wu;Chang Liu;Anjali Sharma;Wathsala Liyanage;Zaver M. Bhujwalla;Marie-France Penet Vidaver;Rangaramanujam M. Kannan;Stavroula Sofou - 通讯作者:
Stavroula Sofou
Artificial neural network detection of pancreatic cancer from proton (1H) magnetic resonance spectroscopy patterns of plasma metabolites
基于血浆代谢物质子(1H)磁共振波谱模式的胰腺癌人工神经网络检测
- DOI:
10.1038/s43856-024-00727-0 - 发表时间:
2025-01-21 - 期刊:
- 影响因子:6.300
- 作者:
Meiyappan Solaiyappan;Santosh Kumar Bharti;Raj Kumar Sharma;Mohamad Dbouk;Wasay Nizam;Malcolm V. Brock;Michael G. Goggins;Zaver M. Bhujwalla - 通讯作者:
Zaver M. Bhujwalla
Molecular and functional imaging insights into the role of hypoxia in cancer aggression
- DOI:
10.1007/s10555-019-09788-3 - 发表时间:
2019-03-06 - 期刊:
- 影响因子:8.700
- 作者:
Samata Kakkad;Balaji Krishnamachary;Desmond Jacob;Jesus Pacheco-Torres;Eibhlin Goggins;Santosh Kumar Bharti;Marie-France Penet;Zaver M. Bhujwalla - 通讯作者:
Zaver M. Bhujwalla
Zaver M. Bhujwalla的其他文献
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{{ truncateString('Zaver M. Bhujwalla', 18)}}的其他基金
The Tumor Microenvironment in Nanoparticle Delivery and Function
纳米颗粒递送和功能中的肿瘤微环境
- 批准号:
10059035 - 财政年份:2020
- 资助金额:
$ 96.24万 - 项目类别:
The Tumor Microenvironment in Nanoparticle Delivery and Function
纳米颗粒递送和功能中的肿瘤微环境
- 批准号:
10405098 - 财政年份:2020
- 资助金额:
$ 96.24万 - 项目类别:
The Tumor Microenvironment in Nanoparticle Delivery and Function
纳米颗粒递送和功能中的肿瘤微环境
- 批准号:
10170305 - 财政年份:2020
- 资助金额:
$ 96.24万 - 项目类别:
The Tumor Microenvironment in Nanoparticle Delivery and Function
纳米颗粒递送和功能中的肿瘤微环境
- 批准号:
10617333 - 财政年份:2020
- 资助金额:
$ 96.24万 - 项目类别:
Molecular Imaging Reagents for Prostate Cancer Theranostics
用于前列腺癌治疗诊断的分子成像试剂
- 批准号:
10226208 - 财政年份:2017
- 资助金额:
$ 96.24万 - 项目类别:
Molecular Imaging of Cachexia in Pancreatic Cancer
胰腺癌恶病质的分子影像
- 批准号:
9026680 - 财政年份:2015
- 资助金额:
$ 96.24万 - 项目类别:
Decoy nanoparticles to disrupt cancer cell-stromal cell networks
诱饵纳米颗粒破坏癌细胞-基质细胞网络
- 批准号:
9102034 - 财政年份:2015
- 资助金额:
$ 96.24万 - 项目类别:
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