Personalized Medicine: Molecular Imaging, Radionuclide and Proton-Beam Therapy

核医学（NM）成像模式，如单正电子发射断层扫描（PET）和单光子发射断层扫描（SPECT），已经很好地认识到他们的分子特征。它们都使用放射性原子标记的生物活性分子，为医生提供有关患者解剖和/或生理的诊断信息。最近，NM应用已经扩展到包括靶向放射性核素疗法（TRT），其中用治疗剂标记的相同分子用于将治疗递送到先前在诊断研究中确定的位置。* 虽然这里提出的概念（称为治疗诊断学）似乎非常令人兴奋，有望成为疾病治疗的新领域，但这些程序的有效性高度依赖于放射性同位素的正确选择，放射性标记分子在体内的精确定位以及放射性浓度的准确定量。具体而言，为了优化TRT结局并最大限度地减少对健康组织的潜在损伤，应进行准确的个性化剂量测定。不幸的是，与外照射放射治疗相比，TRT剂量测定被认为难以进行，因此在临床上不常规进行。* 我的医学影像研究小组（MIRG）研究计划的主要目标是利用我们在物理学，工程学，数学和计算机科学方面的基础科学专业知识，开发实用和强大的方法，提高NM程序的准确性和有效性。我们专注于在个性化医疗模式中使用放射性同位素分布定量成像的方法，以优化诊断并根据每个患者的需求定制治疗。* 本提案中讨论的项目包括研究新放射性同位素的生产，（用于诊断和治疗），包括旨在优化成像方法的广泛研究（数据采集和定量图像重建）以提供关于肿瘤和器官中的活性分布的定量信息，并跟踪这些分布随时间的变化，精确计算吸收的辐射剂量和该剂量空间分布。在寻找新的诊断和治疗同位素时，我们将努力确定最佳生产条件。同时，我们将致力于优化的实用图像为基础的个性化剂量测定方法TRT使用现有的和新的？然后呢？放射出放射性同位素此外，我们将利用我们的核和医学物理专业知识开发新的成像系统（基于碲锌镉（CZT）的康普顿相机），用于在质子束放射治疗中体内确定质子范围。我们的研究结果将是定量准确的诊断方法和个性化治疗。

Nuclear medicine (NM) imaging modalities, such as single positron emission tomography (PET) and single photon emission tomography (SPECT), are already well recognized for their molecular characteristics. They both use biologically active molecules, labeled with radioactive atoms, to provide physicians with diagnostic information about the anatomy and/or physiology of patients. Recently, NM applications have been extended to include targeted radionuclide therapies (TRT), where same molecules labeled with therapeutic agents are used to deliver treatment to locations previously identified in diagnostic studies. ***Although the concepts presented here (named theranostics) seem extremely exciting, promising a new area in treatment of diseases, the effectiveness of such procedures is highly dependent on the proper selection of radioisotopes, the precise localization of radiolabeled molecules in the body and on the accurate quantification of radioactivity concentrations. Specifically, in order to optimize TRT outcomes and minimize potential damage to healthy tissues, accurate personalized dosimetry should be performed. Unfortunately, in contrast to the external beam radiotherapy, TRT dosimetry is considered difficult to perform therefore not routinely done in clinics. ***The main objective of the research program of my Medical Imaging Research Group (MIRG) is to use our basic science expertise in physics, engineering, mathematics and computer science to develop practical and robust methods that will improve the accuracy and effectiveness of NM procedures. We focus on methods which use quantitative imaging of radioisotope distributions in the personalized medicine' paradigm, in order to optimize diagnosis and customize treatment to each individual patient needs. ***The projects discussed in this proposal range from the investigations of production of the new radioisotopes (for diagnosis and therapy), include extensive research aiming at optimization of the imaging methods (data acquisition and quantitative image reconstructions) to provide quantitative information about activity distributions in tumours and organs, and to track changes of these distributions over time, to accurate calculations of the absorbed radiation dose and this dose spatial distribution. In our search for new diagnostic and therapeutic isotopes we will strive to identify the best production conditions. In parallel, we will work on optimization of the practical image-based personalized dosimetry methods for TRT using existing and new ? and ? emitting radioisotopes. Additionally, we will use our nuclear and medical physics expertise to develop new imaging system (Cadmium Zinc Telluride (CZT)-based Compton camera) for in-vivo determination of proton ranges in proton-beam radiotherapy. The result of our research will be quantitatively accurate methods for diagnosis and personalized therapies.