两种18F标记多肽方法的对比研究

Comparison study of two ^(18)F labeling methods of peptides

具有生物活性的多肽类药物是目前医用放射性诊疗药物研发的一个热点,开辟了核医学分子影像剂的一个新领域。受体特异性的活性肽具有较好的药代动力学特性,且容易进行结构修饰和放射性标记,受到受体显像和肿瘤靶向性定位领域研究人员的广泛关注。一些多肽类放射性药物已经用于临床及临床前试验,且大量的多肽正有待开发。多肽的放射性标记技术经过多年的发展,已经建立起了系统的方法。通过这些方法获得的放射性药物不会影响多肽的生理活性。本文选用了两种18F标记多肽的方法,通过标记条件、放化产率、标记物的比活度、放化纯度、稳定性及荷瘤鼠体内分布等方面对两种标记方法进行比较研究,为18F标多肽类放射性药物的研究提供借鉴。

Background： Some radiopharmaceuticals based on peptides have been applied in preclinical and clinical trials, in the meantime, a large number of peptides are to be exploited. After years of development, radiolabeling techniques of peptides have progressed to be a system method. Through these methods of radiolabeling, peptides＇ physiological activities would be influenced. Purpose： In this paper, we summarized two current commonly used 18F labeling methods for preparation of radiopharmaceuticals based on peptides. Methods： By comparison of labeling conditions, radiochemistry yields, specific activity of labeling products, radiochemistry purity, stability and pharmacokinetics of final products, we evaluated advantages and disadvantages of the two methods, with the hope to provide reference data for future research of 18F-labeled peptide radiopharmaceuticals. Results： Both [18F]SFB and Al18F-NOTA could readily label RGDyk peptide with 18F, with a radiochemistry yield of about 8.5% and 15%, respectively. [18F]SFB could produce radiolabeled peptides with better specific activity, while Al18F-NOTA proved to be a more time-saving method. For stability test, more than 80% of both [18F]SFB and Al18F-NOTA could maintain intact in PBS （Phosphate Buffer Solution） or BSA （Bovine Serum Albumin） within 360 min, and about 50% radiolabeled peptides could survive in vivo. Conclusion： The in vitro and in vivo stability of [18F]-RGD obtained with both methods were excellent, and biodistribution pattern of radiolabeled products via two methods did not show obvious differences.