放射金属组学:以α核素靶向治疗药物为例

Radiometallomics:Taking Targeted α Therapeutic Medicines as an Example

金属组学是综合研究生命体内(特别是细胞内)自由或络合的全部金属和类金属的含量、分布、形态、结构及功能的一门学科。作为金属组学的一个分支,放射金属组学重点研究放射性核素的制备和应用,特别是其在环境和生物体内的含量、分布、化学种态及功能等。靶向α治疗(Targeted alpha therapy,TAT)是一种利用发射α粒子的放射性核素与肿瘤选择性载体分子结合实现靶向癌细胞,进而对肿瘤组织造成杀伤作用的一种医疗方法,是放射金属组学在癌症治疗领域的重要应用方向。α粒子凭借高线性能量传递、短组织射程和较强的相对生物学效应,在放射性免疫和肿瘤治疗方面有着广阔的应用前景。以TAT药物为例,就常用α核素、TAT药物螯合剂及其标记的靶向载体、几种重要α放射性核素靶向治疗进展予以综述,并分析TAT药物研发的挑战和发展前景,从而展示放射金属组学在核医学领域特别是癌症治疗领域的研究进展。随着更多α核素的制备和更多靶向标记方法的建立,TAT药物有望用于多种疾病,这也需要新的放射金属组学方法的建立和应用。因此,放射金属组学在核医学领域具有良好应用前景。

Metallomics is a integrated study of the content,distribution,speciation,structure and functions of all free or complexed metals/metalloids in organisms(especially in cells).As an important branch of metallomics,radiometallomics focuses on the preparation and application of radionuclides,especially their content,distribution,chemical states and functions in the environment and organisms.Targeted alpha therapy(TAT)is a method of utilizing the combination of radionuclides emitting alpha particles and tumor selective carrier molecules as a specific targeted cancer cell carrier to target tumor cells,thereby causing a killing effect on tumor tissue,which is an important application direction of radiometallomics in the field of cancer treatment.With high linear energy transfer,short tissue range and strong relative biological effect,αparticles have greater application potential in radioimmunoassay and tumor treatment.Taking TAT drug as an example,the advances in targeted therapy ofα-nuclide commonly used,TAT drug chelating agent and its labeled targeting carrier,and several importantα-radionuclides were reviewed in this paper.In addition,the challenges and development prospects of TAT drug research and development were also analyzed.With the availability of moreαnuclides and the development of new targeting ligands,TAT drugs can potentially be applied to treat other diseases,This also requires the establishment and application of new radiometallomics methods.Therefore,radiometallomics has good application perspective in the field of nuclear medicine.