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在治疗期间和治疗后监测患者方面发挥着重要作用。成像在癌症研究中也是一个重要的工具，它被用来提高我们对癌症生物学的理解，并在临床前研究中对新治疗策略的效果进行纵向评估。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，对抗击癌症至关重要。成像技术的进步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。影像将在介入癌症治疗中进一步深入，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开功能区，尽可能实现无癌边缘。我们还预计，通过更快、更低成本的成像，以及通过减少辐射剂量，成像研究将增强癌症成像，从而使成像更容易获得，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记物的开发，通常与靶向治疗有关，将是为这些进展提供基础的关键。因此，在各个层面对癌症成像的进一步投资可能会产生很高的回报。光学对比剂或放射性示踪剂的分子成像提供了一些可用的体内最高灵敏度的分析方法，并提供了丰富的对比剂机制来源。在这项提议中，我们在生物医学成像领域25年的跟踪记录的基础上，提议利用位于光子学和辐射科学的交叉点上的癌症成像和癌症治疗学的新机会。我们提出的初步项目是：1)提供利用超声调制切伦科夫发光对放射性核素进行高分辨率光学成像的前景；2)使光能够定向传递到体内深处的肿瘤，从而使光疗成为转移疾病的系统性治疗；3)利用正电子发射断层扫描(PET)探测器中瞬时产生的光学切伦科夫光子，目标是显著提高正电子发射断层扫描(PET)成像的时间分辨率和信噪比。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(通过改进的诊断、分期或治疗)或间接(通过癌症研究的贡献)造福于癌症患者。

 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.