Towards Personalized Medicine: Molecular Imaging and Internal Radiotherapy

生物、化学和物理方面的最新进展为推进许多疾病的治疗提供了前所未有的机会，方法是在“个人化医学”模式中使用放射性药物。核医学(NM)成像技术，如正电子发射计算机断层扫描(PET)和SPECT，已经因其分子特性而得到广泛认可。这两种技术都依赖于使用标记有放射性同位素的生物活性分子，为医生提供有关患者解剖和/或生理的诊断信息。这不仅有助于诊断疾病，还允许医生定位分子受体位置，研究疾病细胞表达的生物标记物，并监测特定疾病过程的存在和/或程度。此外，在靶向内放射治疗(IRT)中，标记了治疗剂的相同分子被用于将治疗输送到先前在诊断性研究中确定的位置。 然而，这些医疗程序的有效性高度依赖于放射性标记分子定位的准确性和对其浓度的定量测量的准确性。特别是，为了优化IRT结果并将对健康组织的潜在损害降至最低，必须进行准确的剂量计算。然而，由于常规成像研究中放射性示踪剂分布测量的精度有限，这些计算仍然非常具有挑战性。因此，通常不执行剂量测定，或者只使用对投放剂量的粗略估计。 我的医学成像研究小组(MIRG)的研究计划的主要目标是利用先进的物理、数学和计算机科学来开发适用于日常临床实践以及医学和分子研究的诊断和治疗核医学的新的和改进的方法。本申请中提出的项目利用物理原理并在过去MIRG研究的基础上开发新技术，这将有助于将常规临床实践推进到个性化医学时代。

Recent progress in biology, chemistry and physics has open up unprecedented opportunities to advance the treatment of many diseases by employing radiopharmaceuticals in a "personalized medicine" paradigm. Nuclear medicine (NM) imaging techniques, such as PET and SPECT, are already well recognized for their molecular characteristics. Both techniques rely on the use of biologically active molecules, labeled with radioactive isotopes, to provide physicians with diagnostic information about the anatomy and/or physiology of patients. This not only helps to diagnose diseases, but also allows doctors to locate molecular receptor sites, study biological markers expressed by diseased cells, and monitor the presence and/or extent of specific disease processes. Additionally, in targeted internal radiotherapy (IRT), the same molecules labeled with therapeutic agents are used to deliver treatment to locations previously identified in diagnostic studies. The effectiveness of these medical procedures is, however, highly dependent both on the accuracy of localization of radiolabeled molecules and on the accuracy of quantitative measurement of their concentrations. In particular, to optimize IRT outcomes and minimize potential damage to healthy tissues, accurate dosimetry calculations must be performed. These calculations, however, remain very challenging due to the limited accuracy of radiotracer distribution measurements in routine imaging studies. As a result, dosimetry is often not performed or only crude estimates of delivered doses used. The main objective of the research program of my Medical Imaging Research Group (MIRG) is to use advanced physics, mathematics and computer science to develop new and improved methods for diagnostic and therapeutic nuclear medicine suitable for use both in everyday clinical practice and in medical and molecular research. The projects presented in this application utilize physics principles and build on past MIRG research to develop new techniques which should help to advance routine clinical practice to the personalized medicine era.