Multimodal Qdot Probes for Bioimaging of Cells and Tumors in Small Animals

用于小动物细胞和肿瘤生物成像的多模式 Qdot 探针

• 批准号: 7891424
• 负责人: SHIMON WEISS
• 金额: $ 85.45万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7891424
• 关键词: Animal Experiments; Animal Model; Animals; Antibodies; Arts; Asses; Behavior; Biodistribution; Biological; Biomedical Engineering; Cancer Biology; Cancer Model; Cancer Patient; Cancerous; Cells; Chelating Agents; Chemistry; Clinical; Clinical Management; Clinical Trials; Coupled; Detection; Development; Diagnosis; Diagnostic; Disease Management; Drug Delivery Systems; Early Diagnosis; Electron Microscopy; Electronics; Evaluation; Fluorescence; Funding; Future; Gene Combinations; Gene Expression Profiling; Goals; Human; Image; Imaging Device; Imaging technology; Institutes; Interdisciplinary Study; Karyotype determination procedure; Label; Lead; Life; Ligation; Malignant Neoplasms; Microscope; Microscopy; Mission; Modality; Modeling; Modification; Molecular; Molecular Evolution; Monitor; Multiphoton Fluorescence Microscopy; National Cancer Institute; Noise; Nucleic Acids; One-Step dentin bonding system; Optical Instrument; Optics; Output; Peptide Library; Peptide antibodies; Peptides; Performance; Pharmacology; Physicians; Physics; Positron-Emission Tomography; Process; Prognostic Marker; Property; Quantum Dots; Recovery; Research; Research Personnel; Resolution; Sampling; Science; Scientist; Semiconductors; Signal Transduction; Specimen; Surface; System; Technology; Therapeutic; Time; Tissues; Toxic effect; Tumor Markers; Validation; Work; abstracting; antibody engineering; bioimaging; cancer cell; cellular imaging; clinical application; density; drug discovery; fluorophore; imaging probe; improved; instrumentation; molecular imaging; mouse model; multi-photon; multidisciplinary; multimodality; nanocrystal; nanometer; neoplastic cell; next generation; novel; novel strategies; outcome forecast; pre-clinical; programs; single molecule; tomography; tool; tumor; tumor progression; validation studies

DESCRIPTION (provided by applicant): Quantum dots (qdots) have emerged as new fluorescent, non-isotopic labels that are thought to have unmatched potentials as novel intravascular probes for both diagnostic (e.g., biological imaging) and therapeutic purposes (e.g., drug delivery). This application capitalizes on the progress we have made in the first 5 years of BRP funding, aiming to bring qdots one step closer to routine use in pre-clinical and clinical models. Towards this goal, we will perform detailed validation studies of targeted qdots in living mice models that are already impacting clinical management of cancer patients by using small animal imaging technologies including multiphoton microscopy and fluorescence tomography. During the next 5 years of this project, we will (1) develop and bioconjugate new multimodal contrasting qdot agents; (2) develop new optical instruments for near infrared (NIR) qdot detection and (3) perform validation studies of targeted qdots in cells and animals. We will focus on cancer where no single imaging agent can provide adequate information for diagnosis, prognosis and treatment decisions. Rather, a better understanding of the biological behavior and potential of malignant cells is inherent to new instrumentations and probes that will allow multiplex imaging of panels of targets/markers. The availability of NIR qdots with several output wavelengths, coupled with tumor marker-specific engineered antibodies, peptides or nucleic acids, will streamline multicolor/ marker imaging of cells and tumors. We will develop panels of qdot probes useful for karyotyping cancerous cells and for gene expression profiling towards a combination of genes that would be diagnostic or prognostic markers for cancer progression. Using cancer models, we will visualize the bio-distribution of qdots at all scales, from the level of the whole animal body down to nanometer resolution using a single probe by combining the micro-PET and optical modalities of antibody-functionalized NIR qdots. We will also asses toxicity and size effects on biodistribution of these probes. Our multidisciplinary team of 5 investigators with expertise in physics, chemistry, materials sciences, bioengineering, pharmacology, imaging and cancer biology should help to more rapidly validate this new exciting class of imaging probes for eventual clinical applications. Lay abstract: Physicians can now monitor tumors and malignant cells deep within our body. Our research aims at validating new sensitive probes (known as Quantum Dots, or qdots) for non-invasive tumor imaging in animal models. The unique properties of qdots might afford in the future earlier diagnosis and better management of disease in humans.

描述（由申请人提供）：量子点 (qdot) 已成为新型荧光非同位素标记，被认为作为新型血管内探针具有无与伦比的潜力，可用于诊断（例如生物成像）和治疗目的（例如药物输送） ）。该应用利用了我们在 BRP 资助的前 5 年中取得的进展，旨在使 qdot 更接近临床前和临床模型中的常规使用。为了实现这一目标，我们将通过使用包括多光子显微镜和荧光断层扫描在内的小动物成像技术，对活体小鼠模型中的靶向量子点进行详细的验证研究，这些模型已经影响了癌症患者的临床管理。在该项目的未来 5 年中，我们将 (1) 开发和生物共轭新的多模式对比 qdot 试剂； (2) 开发用于近红外 (NIR) 量子点检测的新型光学仪器，以及 (3) 对细胞和动物中的目标量子点进行验证研究。我们将重点关注癌症，没有任何一种成像剂可以为诊断、预后和治疗决策提供足够的信息。相反，更好地了解恶性细胞的生物学行为和潜力是新仪器和探针所固有的，这些仪器和探针将允许对目标/标记物组进行多重成像。具有多种输出波长的近红外量子点的可用性，加上肿瘤标志物特异性工程抗体、肽或核酸，将简化细胞和肿瘤的多色/标志物成像。我们将开发可用于癌细胞核型分析和基因表达谱分析的 qdot 探针组，以作为癌症进展的诊断或预后标记的基因组合。使用癌症模型，我们将通过结合抗体功能化 NIR 量子点的微型 PET 和光学模式，使用单个探针可视化所有尺度的量子点生物分布，从整个动物体的水平到纳米分辨率。我们还将评估这些探针生物分布的毒性和尺寸影响。我们的多学科团队由 5 名研究人员组成，他们拥有物理、化学、材料科学、生物工程、药理学、成像和癌症生物学方面的专业知识，应该有助于更快地验证这一令人兴奋的新型成像探针的最终临床应用。摘要：医生现在可以监测我们身体深处的肿瘤和恶性细胞。我们的研究旨在验证新的敏感探针（称为量子点或 qdot）在动物模型中用于非侵入性肿瘤成像。量子点的独特特性可能在未来提供对人类疾病的早期诊断和更好的管理。

项目成果

Quantum dots for in vivo small-animal imaging.

• DOI: 10.2967/jnumed.108.053561
• 发表时间: 2009-04
• 期刊: Journal of nuclear medicine : official publication, Society of Nuclear Medicine
• 作者: Bentolila LA;Ebenstein Y;Weiss S
• 通讯作者: Weiss S

Near-infrared peptide-coated quantum dots for small animal imaging.

用于小动物成像的近红外肽涂层量子点。

• DOI: 10.1117/12.661777
• 发表时间: 2006
• 期刊: Proceedings of SPIE--the International Society for Optical Engineering
• 作者: Iyer,Gopal;Li,JackJ;Pinaud,Fabien;Tsay,JamesM;Bentolila,LaurentA;Michalet,Xavier;Weiss,Shimon
• 通讯作者: Weiss,Shimon

Hybrid approach to the synthesis of highly luminescent CdTe/ZnS and CdHgTe/ZnS nanocrystals.

• DOI: 10.1021/ja039227v
• 发表时间: 2004-01
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: J. Tsay;M. Pflughoefft;L. Bentolila;S. Weiss

Suppression of quantum dot blinking in DTT-doped polymer films.

• DOI: 10.1021/jp811078e
• 发表时间: 2009-03-31
• 期刊: The journal of physical chemistry. C, Nanomaterials and interfaces
• 作者: Antelman J;Ebenstein Y;Dertinger T;Michalet X;Weiss S
• 通讯作者: Weiss S

Toward single-molecule optical mapping of the epigenome.

• DOI: 10.1021/nn4050694
• 发表时间: 2014-01-28
• 期刊: ACS nano
• 影响因子: 17.1
• 作者: Levy-Sakin M;Grunwald A;Kim S;Gassman NR;Gottfried A;Antelman J;Kim Y;Ho SO;Samuel R;Michalet X;Lin RR;Dertinger T;Kim AS;Chung S;Colyer RA;Weinhold E;Weiss S;Ebenstein Y
• 通讯作者: Ebenstein Y