Scientific Developments in Imaging and Dosimetry for Molecular Radiotherapy

Molecular radiotherapy is a rapidly developing field with new vector and isotope combinations continually added to market. As with any radiotherapy treatment, it is vital that the absorbed dose and toxicity profile are adequately characterised. Methodologies for absorbed dose calculations for radiopharmaceuticals were generally developed to characterise stochastic effects and not suited to calculations on a patient-specific basis. There has been substantial scientific and technological development within the field of molecular radiotherapy dosimetry to answer this challenge. The development of imaging systems and advanced processing techniques enable the acquisition of accurate measurements of radioactivity within the body. Activity assessment combined with dosimetric models and radiation transport algorithms make individualised absorbed dose calculations not only feasible, but commonplace in a variety of commercially available software packages. The development of dosimetric parameters beyond the absorbed dose has also allowed the possibility to characterise the effect of irradiation by including biological parameters that account for radiation absorbed dose rates, gradients and spatial and temporal energy distribution heterogeneities. Molecular radiotherapy is in an exciting time of its development and the application of dosimetry in this field can only have a positive influence on its continued progression.     

检测乙酰胆碱酯酶的双光子荧光探针的设计、合成及生物学评价

目的 设计并合成用于检测乙酰胆碱酯酶（acetylcholinesterase，AChE）的双光子荧光探针，并考察探针对AChE的成像检测性能。方法 经酯化、取代等多步有机反应合成探针，并通过¹H-NMR、¹³C-NMR和ESI-MS确认结构。考察探针与AChE发生响应后的荧光信噪比、灵敏度、特异性、酶动力学和双关子吸收截面积数值等指标；研究探针可否用于AChE抑制剂的体外筛选；利用单-双光子成像试验考察探针在细胞和组织水平上对AChE活力变化的检测能力。结果 通过¹H-NMR、¹³C-NMR和ESI-MS确认了产物的结构。体外试验表明探针与AChE响应后的荧光信噪比为15倍，检测限达到0.23 U·mL^–1，并具有很强的特异性和优良的酶亲合能力，在波长820 nm有最优的双光子吸收；探针可用于AChE抑制剂的体外筛选；探针通过单-双光子成像技术可对细胞和组织水平上的AChE活力变化进行成像检测，并且组织成像检测深度可达110 μm。结论 本研究成功开发了可用于AChE检测的双光子荧光探针，有潜力成为可用于活体中检测AChE活力的双光子成像试剂。