Research at the interface of optical and ionizing radiation for innovative cancer imaging and therapy

 描述（由申请人提供）：成像通常是癌症筛查、检测、诊断和分期的基础。它还在癌症治疗计划以及治疗期间和治疗后监测患者方面发挥重要作用。成像也是癌症研究中的重要工具，用于提高我们对癌症生物学的理解，并用于临床前研究中新治疗策略效果的纵向评估。进一步发展现有的成像技术，以及发明或发现新的成像技术，在与癌症的斗争中至关重要。成像技术的改进将帮助我们更早地发现疾病，更准确地对癌症进行分期，选择更合适的治疗方法，并在治疗无效时提供更早的反馈。影像学将在介入性癌症治疗中变得更加根深蒂固，特别是在外科手术中，迫切需要更好的方法来指导外科医生在切除过程中避免功能区并尽可能实现无癌边缘。我们还期望成像研究通过更快和更低成本的成像以及通过减少辐射剂量来增强癌症成像，从而使成像更广泛地获得，并提高患者的舒适度和安全性。在实验室环境中，能够在适当的动物模型中改善肿瘤的结构，功能和分子特征的仪器，以及新的成像生物标志物的开发，通常与靶向治疗有关，将为这些进展提供基础。因此，在各级癌症成像方面的进一步投资可能会产生很高的回报。 具有光学对比或放射性示踪剂的分子成像提供了一些可用的最高灵敏度的体内测定，并且提供了对比机制的丰富来源。在这项提案中，我们建立在我们在生物医学成像领域25年的跟踪记录，并建议利用光子学和辐射科学交叉点的癌症成像和癌症治疗诊断学的新机会。我们提出了初步的计划，1）提供前景的高分辨率光学成像的放射性核素使用超声调制的切伦科夫发光; 2）能够将光靶向递送到身体深处的肿瘤，允许光疗作为转移性疾病的全身治疗应用，以及3）利用正电子发射断层扫描（PET）中光学切伦科夫光子的瞬时产生探测器，其目标是显著提高PET成像中的定时分辨率和信噪比。 该提案的方法是创建和支持一个研究环境，使我们的实验室能够快速测试和开发新的想法，目标是有效地开发创新的癌症成像和治疗策略，这些策略将直接（通过改进诊断，分期或治疗）或间接（通过癌症研究的贡献）使癌症患者受益。

 DESCRIPTION (provided by applicant): Imaging is often fundamental to screening, detection, diagnosis and staging of cancer. It also plays significant roles in cancer treatment planning, and in monitoring patients during and after therapy. Imaging also is a vital tool in cancer research, where it is used to improve our understanding of cancer biology and in the longitudinal evaluation of the effects of new therapeutic strategies in preclinical studies. Further development of existing imaging technologies, as well as the invention or discovery of new ones, is critical in the fight against cancer. Improvements in imaging technologies will help us detect disease earlier, stage cancer more accurately, select more appropriate treatments and provide earlier feedback when a treatment is not working. Imaging will become further engrained in interventional cancer therapies, especially in surgery where there is an urgent need for better methods to guide surgeons during resection to avoid functional areas and achieve cancer-free margins wherever possible. We also expect imaging research to enhance cancer imaging through faster and lower cost imaging, and by reducing radiation dose, thus making imaging more widely accessible, and enhancing patient comfort and safety. In the laboratory setting, instruments capable of improved structural, functional and molecular characterization of tumors in appropriate animal models, as well as the development of new imaging biomarkers, often linked with targeted therapies, will be critical in providing the foundation for these advances. Thus further investments in cancer imaging at all levels are likely to yield a high pay off. Molecular imaging with optical contrast or radiotracers provides some of the highest sensitivity in vivo assays available, and offers a rich source of contrast mechanisms. In this proposal we build on our 25-year track record in the field of biomedical imaging and propose to exploit new opportunities for cancer imaging and cancer theranostics that lie at the intersection of photonics and radiation science. We propose initial projects that 1) offer the prospect of high-resolution optical imaging of radionuclides using ultrasound-modulation of Cerenkov luminescence; 2) enable targeted delivery of light to tumors deep inside the body allowing phototherapy to be applied as a systemic treatment for metastatic disease and 3) exploit the instantaneous generation of optical Cerenkov photons in positron emission tomography (PET) detectors with the goal of significantly improving the timing resolution and the signal-to-noise ratio in PET imaging. The approach in this proposal is to create and support a research environment that allows our laboratory to rapidly test and develop new ideas, with a goal of efficiently developing innovative cancer imaging and therapeutic strategies that will either directly (through improved diagnosis, staging or therapy), or indirectly (via contributions o cancer research) benefit cancer patients.