Molecular Fluorescence-Guided Surgery Platform

分子荧光引导手术平台

• 批准号: 8649029
• 负责人: KEITH D. PAULSEN
• 金额: $ 55.02万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-08 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8649029
• 关键词: Advanced Development; Aminolevulinic Acid; Animal Model; Animals; Binding; Biological; Biological Assay; Biological Markers; Biomedical Engineering; Cell Surface Receptors; Clinical; Clinical Trials; Contrast Media; Detection; Development; Development Plans; Discipline of Nuclear Medicine; Disease; Dose; Drug Kinetics; Engineering; Epidermal Growth Factor Receptor; Excision; Fluorescence; Fluorescent Dyes; Glioma; Human; Image; Injection of therapeutic agent; Institution; Intellectual Property; Investigational Drugs; Malignant Neoplasms; Methods; Microscope; Modality; Molecular; Molecular Probes; New Drug Approvals; North America; Nuclear; Operative Surgical Procedures; Oral; Outcome; Pathway interactions; Patients; Peptide Synthesis; Peptides; Pharmaceutical Preparations; Phase; Positioning Attribute; Positron-Emission Tomography; Procedures; Process; Production; Proteins; Recurrence; Research Infrastructure; Resected; Risk; Series; Signal Transduction; Specificity; Specimen; Strategic Planning; Surgical Oncology; Technology; Testing; Time; Toxicity Tests; Tracer; Translations; Xenograft procedure; absorption; base; brain tumor resection; cost; cost effective; efficacy testing; experience; fluorescence imaging; fluorophore; in vivo; industry partner; medical schools; molecular imaging; neurosurgery; novel; oncology; pre-clinical; primary outcome; protoporphyrin IX; public health relevance; single photon emission computed tomography; success; tumor

DESCRIPTION (provided by applicant): This Academic-Industrial Partnership (AIP) for the development and translation of molecularly-targeted optically-fluorescent imaging agents, GMP-produced for guiding surgical resection in phase 0 clinical trials. While recent advances in the technology for guiding surgical oncology will establish an efficient pipeline have been impressive, significant limitations remain in determining, intraoperatively, the biological margins of disease. Fluorescence-guided surgical resection based on protoporphyrin IX production in high-grade gliomas has highlighted the potential promise of the approach to the extent that intraoperative fluorescence imaging, with both red and infrared channels, is now available on state-of-the-art surgical microscopes manufactured by Leica and Zeiss. Despite these rapid advances, development of the molecular tracers that are required to guide surgical procedures has been lacking. The basis of this application and the underlying tenet of the proposed AIP are that a cost-effective, risk-diluted approach to and cost-effective testing contrast agent development and are needed in order to realize the promise of fluorescence-guidance during surgery. The testing will be carried out with end-points of surgical testing in phase 0 micro dosing studies signal detection and binding specificity being the primary outcomes from the phase 0 trials. Rapid testing is critical because most agents will not be successful, and we need a strategy to reduce the time, cost and risk required to quickly assess targeting efficacy in early human surgical trials. Creation of such a pipeline process stands to accelerate dramatically the paradigm shift to molecular-guided surgical oncology that will revolutionize both the procedures that are possible and the surgical outcomes that will result. The proposed AIP between Dartmouth (Engineering and Medical Schools), Affibody AB, and LI-COR brings together 3 partners who have the intellectual property (IP), expertise and infrastructure to develop, test and advance molecularly-targeted fluorescent tracers for surgical guidance. The first agent we will advance will be an affibody molecule (created and extensively characterized in animals by Affibody, AB, and currently undergoing nuclear imaging studies in humans) targeted to the epidermal growth factor receptor (EGFR) conjugated with a fluorescent dye (systematically developed by LI-COR for human use) with absorption and emission spectra in the near infrared. The compound will be developed and produced through peptide synthesis under GMP conditions, single administration toxicity testing in requisite animal models will be completed, and a first-in-human phase 0 dose escalation study will be pursued at Dartmouth under exploratory investigational new drug (eIND) approval from the FDA.

描述（由申请人提供）：该学术-工业合作伙伴关系（AIP）用于开发和翻译分子靶向光学荧光显像剂，gmp生产用于指导0期临床试验的手术切除。虽然指导外科肿瘤学的最新技术进步将建立一个有效的管道，但在确定术中生物边缘方面仍然存在显着的局限性