New tools for imaging: diagnostics based on therapeutics

成像新工具：基于治疗的诊断

基本信息

批准号：
9102100
负责人：
Pedro Brugarolas
金额：
$ 8.37万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9102100
关键词：
4-Aminopyridine Accounting Affect Affinity Amino Acids Animal Model Antibodies Area Autoimmune Process Award Axon Binding Blood Circulation Caring Cellular biology Clinical Trials Custom Demyelinations Development Diagnosis Diagnostic Imaging Disease Disease Progression Dose Drug Prescriptions Fc domain Fluorine Funding Goals Growth Health Human Image Imaging Device Immune response Immunofluorescence Immunologic Isotopes Label Life Location Low Dose Radiation Magnetic Resonance Imaging Marketing Medicine Methodology Molecular Weight Monitor Monoclonal Antibodies Monoclonal Antibody Therapy Multiple Sclerosis Myelin National Institute of Neurological Disorders and Stroke Neuraxis Neurologic Neurons Paper Patient Care Patients Peptides Phage Display Pharmaceutical Preparations Pharmacodynamics Pharmacologic Substance Phase Physicians Positron Positron-Emission Tomography Potassium Channel Property Proteins Radiation Radioactive Scanning Sensitivity and Specificity Specificity Structure System Techniques Technology Therapeutic Therapeutic Monoclonal Antibodies Therapeutic antibodies Time Tracer Training Voltage-Gated Potassium Channel antibody engineering base channel blockers cost design drug market imaging biomarker imaging system immunogenicity improved in vivo myelination nervous system disorder novel novel therapeutics precision medicine predicting response protein aminoacid sequence remyelination research study response small molecule success therapy development therapy outcome tool uptake white matter young adult

项目摘要

DESCRIPTION (provided by applicant): Sensitive and specific tools to diagnose and monitor diseases are crucial. In the first part of this application (K99), I describe my current postdoctorl project to develop a PET tracer for multiple sclerosis (MS); a common neurological condition that affects young adults. This tracer binds to axonal voltage gated K+ channels that have been exploited for therapy but never for imaging. Unlike the tracers for myelin developed to date, this tracer has low baseline uptake in white matter that increases upon demyelination, making it a very promising tool to monitor changes in myelination. Such a tool could improve how MS is monitored and diagnosed and provide the necessary endpoints to evaluate new therapies that promote remyelination. Using the principles and expertise acquired on this project, I propose to develop a new tool for imaging monoclonal antibodies (mAbs) using PET that does not involve radioactive antibodies (R00). This will be accomplished by adding to the antibody a short peptide that is designed to recognize a small molecule tracer. Because small molecules have much faster pharmacodynamics than antibodies this offers the possibility of using short-lived isotopes like F-18 and low doses of radiation. In the dawn of the therapeutic monoclonal antibody era a general tool to visualize and predict response to mAb therapies has the potential to improve patient care and decrease costs associated with these therapies.

描述（由申请人提供）：诊断和监测疾病的敏感且具体的工具至关重要。在本申请的第一部分（K99）中，我描述了我目前的博士后项目，旨在开发一种常见的多发性硬化症（MS）的 PET 示踪剂。该示踪剂与轴突电压门控 K+ 通道结合，已用于治疗，但与迄今为止开发的髓磷脂成像示踪剂不同，该示踪剂具有较低的浓度。脱髓鞘时白质的基线摄取增加，使其成为监测髓鞘变化的非常有前途的工具，这种工具可以改善多发性硬化症的监测和诊断方式，并提供必要的终点来评估促进髓鞘再生的新疗法。凭借在该项目中获得的专业知识，我建议开发一种使用 PET 成像单克隆抗体 (mAb) 的新工具，该工具不涉及放射性抗体 (R00)，这将通过在抗体中添加设计的短肽来实现。由于小分子的药效学比抗体快得多，因此在治疗性单克隆抗体时代的初期，使用 F-18 等短寿命同位素和低剂量辐射成为可能。并预测单克隆抗体疗法的反应有可能改善患者护理并降低与这些疗法相关的成本。