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

核医学(NM)成像方式，如单正电子发射断层扫描(PET)和单光子发射断层扫描(SPECT)，已经因其分子特性而得到广泛认可。它们都使用标记有放射性原子的生物活性分子，为医生提供有关患者解剖和/或生理的诊断信息。最近，NM的应用已扩展到包括靶向放射性核素疗法(TRT)，即使用标记有治疗剂的相同分子将治疗输送到先前诊断研究中确定的位置。 尽管这里提出的概念(称为放射治疗学)似乎非常令人兴奋，有望在疾病治疗中开辟一个新的领域，但此类程序的有效性高度依赖于对放射性同位素的适当选择、体内放射性标记分子的精确定位以及对放射性浓度的准确量化。具体地说，为了优化TRT的结果并将对健康组织的潜在损害降至最低，应该进行准确的个性化剂量测量。不幸的是，与外照射相比，TRT剂量学被认为很难进行，因此不能在临床上常规进行。 我的医学影像研究小组(MIRG)的研究计划的主要目标是利用我们在物理、工程、数学和计算机科学方面的基础科学专业知识来开发实用和可靠的方法，以提高NM程序的准确性和有效性。我们专注于在个性化医学的范例中使用放射性同位素分布的定量成像的方法，以便根据每个患者的需求来优化诊断和定制治疗。 本提案中讨论的项目范围从研究新的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(数据获取和定量图像重建)的广泛研究，以提供关于肿瘤和器官内放射性分布的定量信息，并跟踪这些分布随时间的变化，到准确计算吸收辐射剂量和这种剂量的空间分布。在我们寻找新的诊断和治疗同位素的过程中，我们将努力确定最佳生产条件。同时，我们将致力于优化实用的基于图像的个性化剂量测量方法，利用现有的和新的？然后呢？释放放射性同位素。此外，我们将利用我们的核物理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)，用于在体内确定质子束放射治疗中的质子射程。我们的研究结果将成为诊断和个性化治疗的定量准确方法。

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.