Preclinical PET imaging of HIP/PAP using 1'-(18)F-fluoroethyl-β-D-lactose.
Preclinical PET imaging of HIP/PAP using 1'-(18)F-fluoroethyl-β-D-lactose.
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DOI：
10.18632/oncotarget.20654
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发表时间：
2017-09-26
期刊：
影响因子：
--
通讯作者：
Li F
中科院分区：
文献类型：
--
作者：
Yao S;Luo Y;Zhang Z;Hu G;Zhu Z;Li F
本研究旨在评价最近报道的乳糖类似物18 F-氟乙基-β-D-乳糖（18 F-FEL）与肝癌-肠-胰腺和胰腺炎相关蛋白（HIP/PAP）的体外和体内结合的临床前评价。在这项研究中，一个多功能模块用于自动化合成18F-FEL。使用T3 M4和SK-BR-3异种移植物进行了额外的放射化学纯度、生物分布、体外和体内竞争、代谢稳定性和微型PET研究。用免疫组化（IHC）和western blot分析HIP/PAP在T3 M4和SK-BR-3肿瘤切片和细胞系中的表达。18F-FEL的合成在30 min内完成，放化产率为20 ± 5%，比活度为14.2 ± 7.1 GBq/μmol。18F-FEL表现出高的HIP/PAP结合亲和力，半数最大抑制浓度（IC 50）为22.0 ± 4.0 nM。18F-FEL表现出高稳定性和特异性肿瘤蓄积，通过共注射β-D-乳糖，在PET竞争测定中其减少约80%。HIP/PAP在T3 M4肿瘤和细胞系中呈高表达，而在SK-BR-3细胞系中呈阴性表达。18F-FEL具有与HIP/PAP的高结合特性、高稳定性和优异的体内药代动力学，因此需要在人体概念验证研究中进行进一步评价。
This study aims at preclinical evaluation of a recently reported lactose analogue, 1'-18F-fluoroethyl-β-D-lactose (18F-FEL), in binding to hepatocarcinoma-intestine-pancreas and pancreatitis-associated protein (HIP/PAP) in vitro and in vivo. In this study, a multifunctional module was employed for the automated synthesis of 18F-FEL. Additional radiochemical purity, biodistribution, in vitro and in vivo competition, metabolic stability and micro-PET studies were performed using T3M4 and SK-BR-3 xenografts. Expression of HIP/PAP in T3M4 and SK-BR-3 tumor sections and cell lines were tested with immunohistochemistry (IHC) and western blot analysis. The synthesis of 18F-FEL was completed in 30 min, with a radiochemical yield of 20 ± 5% and specific activity of 14.2 ± 7.1 GBq/μmol. 18F-FEL exhibited high HIP/PAP-binding affinity with a half maximal inhibitory concentration (IC50) of 22.0 ± 4.0 nM. 18F-FEL demonstrated high stability and specific tumor accumulation, which was reduced by approximately 80% in a PET competition assay by co-injection of β-D-lactose. High expression of HIP/PAP was detected in T3M4 tumors and cell line, but negative result was found for SK-BR-3 cell line. 18F-FEL has a high binding property to HIP/PAP, high stability and excellent pharmacokinetics in vivo and therefore warrants further evaluation in a proof-of-concept study in humans.
优化 1'-[18F]氟乙基-β-D-乳糖 ([18F]FEL) 的前体合成、配方和稳定性，用于检测胰腺癌的临床前研究。
影响因子：
3.1
作者：
Paolillo V;De Palatis L;Alauddin MM
通讯作者：
Alauddin MM
影响因子：
1.8
作者：
Turkman, Nashaat;Gelovani, Juri G.;Alauddin, Mian M.
通讯作者：
Alauddin, Mian M.