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Advancing molecular fluorescence-guided surgery platform

先进的分子荧光引导手术平台

基本信息

批准号：
10598545
负责人：
KEITH D. PAULSEN
金额：
$ 54.79万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-08 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10598545
关键词：
Acceleration Adverse effects Aminolevulinic Acid Animal Model Biological Sciences Clinical Clinical Research Custom Data Detection Development Diagnostic Disease Dose EGFR Protein Overexpression Engineering Epidermal Growth Factor Receptor Excision Fluorescence Fluorescent Dyes Funding Glioma Goals Good Manufacturing Process Head and Neck Cancer Head and Neck Squamous Cell Carcinoma Human Image Imaging technology In Situ Industrialization Infiltration Infrastructure Intellectual Property Investigational Drugs Investigational New Drug Application Left Limb structure Malignant Neoplasms Methodology Microscope Molecular Molecular Target Names New Drug Approvals No-Observed-Adverse-Effect Level Oncology Operative Surgical Procedures Pathway interactions Patient-Focused Outcomes Patients Peptides Performance Pharmaceutical Preparations Phase Phase 0 Clinical Trial Phase 0 Trial Phase II Clinical Trials Probability Procedures Productivity Protocols documentation Randomized Research Personnel Resectable Residual state Risk Safety Secondary to Sensitivity and Specificity Signal Transduction Soft tissue sarcoma Solid Neoplasm Structure Surgical Oncology Surgical margins System Testing Tissue imaging Tissues Toxic effect Toxicity Tests Tracer Translating Translations Tumor Tissue Work bench to bedside carboxylate carboxylation clinical development clinical translation cost cost effective design detection sensitivity drug development efficacy study efficacy testing experience first-in-human fluorescence-guided surgery fluorophore imaging agent imaging capabilities imaging system improved in vivo industry partner instrumentation medical schools minimally invasive neurosurgery novel phase 2 designs phase 2 study phase 2 testing phase 3 study phase II trial pre-clinical preclinical toxicity primary endpoint research clinical testing standard of care success surgery outcome synthetic peptide timeline tumor

项目摘要

ABSTRACT This Academic-Industrial Partnership (AIP) will further the clinical development of fluorescence guided surgery (FGS) through the utilization of the FDA exploratory Investigational New Drug (eIND) pathway. While recent advances in both imaging agents and technology for FGS has been impressive, significant limitations remain in detecting low dose administration of imaging agents and obtaining true molecular contrast between the tumor and normal surrounding tissues. The basis of this application and the underlying tenet of the proposed AIP is that a cost-effective, risk-diluted approach to clinical translation of imaging methodologies is needed in order to realize the promise of FGS. Utilization of our previously developed bench-to-clinic pipeline stands to accelerate surgical oncology to revolutionize both the procedures that are possible and the surgical outcomes that will result. In the first funding cycle our AIP implemented a low-cost testing pipeline for ABY-029, a fluorescent epidermal growth factor receptor-targeted synthetic peptide. We established the necessary protocols to bring ABY-029 from pre-clinical animal models into three Phase 0 clinical trials using the FDA eIND pathway (eIND #122681). We will build upon our previous success to apply for Investigational New Drug (IND) status of ABY-029 for economical, investigator-led Phase II testing of detection accuracy in glioma and head and neck cancers. Sim- ultaneously, we will utilize the pipeline to achieve eIND approval of paired-agent imaging. The proposed AIP between Dartmouth (Engineering and Medical Schools), Affibody AB, LI-COR, and DoseOptics brings together 4 partners who have the intellectual property (IP), expertise and infrastructure to develop, test and advance molecular-targeted fluorescent tracers and imaging systems for surgical guidance. Clinical translation and testing of FGS will be achieved through the completion of the following aims: Aim 1 - Advance near-microdose ABY-029 FGS for resection of primary high-grade glioma in a Phase 2 trial; Aim 2 - Adapt FGS system for minimally invasive resection of head and neck cancers for Phase 2 testing; and Aim 3 - Leverage the Dartmouth fluorescent agent development pipeline to bring quantitative molecular paired- agent imaging (PAI) to Phase 0 trial using a cocktail of ABY-029 and IRDye 680LT carboxylate (pABY-IR680). The translational INNOVATION will include advancement of ABY-029 into Phase II clinical trials, first-in-human implementation of paired-agent imaging for true molecular contrast via the established bench-to-clinic eIND pipe- line, and the integration of a highly sensitive, multi-channel near infrared surgical camera imaging system capa- ble of imaging in full surgical lights. The SIGNIFICANCE of this AIP will be to demonstrate improved margin detection for surgical resection of glioma and head and neck cancers using a low-cost, efficient testing pipeline.

摘要