新型固体靶核素89Zr的制备、标记和临床前应用研究进展

Progress in the Production, Labeling of Novel Solid Target Zirconium-89 and its Preliminary Application in the Preclinical

利用正电子核素标记抗体进行PET免疫显像是筛选适合抗体靶向治疗的重要方法,正电子核素锆-89(89Zr)由于其较长的半衰期使其成为PET免疫显像的理想核素,同时89Zr核素还可用于制备纳米粒子、微球等,其在临床上的应用越来越广泛。本文对固体靶核素89Zr的制备、标记以及临床前应用等进行调研,了解国内外89Zr的制备方法和工艺,探索先进的标记方法,并讨论其在肿瘤临床诊疗的应用价值。

Recently,positron emission tomography/computed tomography(PET/CT)has expanded to become a routine diagnostic study of particular importance in oncology in treatment evaluation and management.In particle,immuno-PET which uses positron nuclide labeled antibodies,antibody fragments,and peptides for the in vivo molecular imaging is one of the most important methods for selecting effective targeted therapy patients.Due to its longer half-life meeting with the body clearance rate of antibodies,positron radionuclide zirconium-89(89Zr)has become the ideal nuclide for immuno-PET.The current most common route to produce 89Zr is via cyclotron through the 89Y(p,n)89Zr nuclear reaction using natural abundance yttrium-89(89Y)foil.Meanwhile,higher activity recovery method for 89Zr using the hydroxamate resin purification has become the standardized method in most paper reports.As DFO is currently the most promising chelator for 89Zr,so it is important to select an adequate conjugation of DFO to an antibody.Over the last years,several 89Zr-labeled antibodies directed against different tumor types have been evaluated in preclinical studies.Furthermore,89Zr can also be used to prepare nanoparticles and microspheres.It has become more and more useful in the clinical application.However,in China,there is no company or institute can provide nuclide 89Zr continually and steadily.So it is very necessary and important to carry out series of researches on the production,purification and conjugation strategies of 89Zr.Accordingly,89Zr based immuno-PET in the preclinical oncology studies will be developed and apply to clinical practice gradually.In this paper,the solid target production methods and isolation of 89Zr are investigated.The antibodies labeling methods and the preclinical application value in cancer are discussed.