18F-radiolabeled analogs of exendin-4 for PET imaging of GLP-1 in insulinoma.
18F-radiolabeled analogs of exendin-4 for PET imaging of GLP-1 in insulinoma.
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DOI：
10.1007/s00259-011-1980-0
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发表时间：
2012-03
影响因子：
9.1
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
--
作者：
Kiesewetter, Dale O.;Gao, Haokao;Ma, Ying;Niu, Gang;Quan, Qimeng;Guo, Ning;Chen, Xiaoyuan
Glucagon-like peptide type 1 (GLP-1) is an incretin peptide that augments glucose-stimulated insulin release following oral consumption of nutrients. Its message is transmitted via a G protein-coupled receptor called GLP-1R, which is colocalized with pancreatic β-cells. The GLP-1 system is responsible for enhancing insulin release, inhibiting glucagon production, inhibiting hepatic gluconeogenesis, inhibiting gastric mobility, and suppression of appetite. The abundance of GLP-1R in pancreatic β-cells in insulinoma, a cancer of the pancreas, and the activity of GLP-1 in the cardiovascular system have made GLP-1R a target for molecular imaging. We prepared 18F radioligands for GLP-1R by the reaction of [18F]FBEM, a maleimide prosthetic group, with [Cys0] and [Cys40] analogs of exendin-4. The binding affinity, cellular uptake and internalization, in vitro stability, and uptake and specificity of uptake of the resulting compounds were determined in an INS-1 xenograft model in nude mice. The [18F]FBEM-[Cysx]-exendin-4 analogs were obtained in good yield (34.3±3.4%, n=11), based on the starting compound [18F]FBEM), and had a specific activity of 45.51±16.28 GBq/μmol (1.23±0.44 Ci/μmol, n=7) at the end of synthesis. The C-terminal isomer, [18F]FBEM-[Cys40]-exendin-4, had higher affinity for INS-1 tumor cells (IC50 1.11±0.057 nM) and higher tumor uptake (25.25±3.39 %ID/g at 1 h) than the N-terminal isomer, [18F]FBEM-[Cys0]-exendin-4 (IC50 2.99±0.06 nM, uptake 7.20±1.26 %ID/g at 1 h). Uptake of both isomers into INS-1 tumor, pancreas, stomach, and lung could be blocked by preinjection of nonradiolabeled [Cysx]-exendin-4 (p<0.05). [18F]FBEM-[Cys40]-exendin-4 and [18F]FBEM-[Cys0]-exendin-4 have high affinity for GLP-1R and display similar in vitro cell internalization. The higher uptake into INS-1 xenograft tumors exhibited by [18F]FBEM-[Cys40]-exendin-4 suggests that this compound would be the better tracer for imaging GLP-1R.
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影响因子：
1.9
作者：
Kiesewetter, Dale O.;Kramer-Marek, Gabriela;Ma, Ying;Capala, Jacek
通讯作者：
Capala, Jacek
DOI：
10.1007/s00259-002-0761-1
发表时间：
2002-05-01
影响因子：
9.1
作者：
Gotthardt, M;Fischer, M;Behr, TM
通讯作者：
Behr, TM
DOI：
10.1016/j.bbrc.2009.09.014
发表时间：
2009-11-20
影响因子：
3.1
作者：
Mukai, Eri;Toyoda, Kentaro;Inagaki, Nobuya
通讯作者：
Inagaki, Nobuya
影响因子：
7.3
作者：
Murage, Eunice N.;Gao, Guangzu;Ahn, Jung-Mo
通讯作者：
Ahn, Jung-Mo
[18F] FBEM的自动放射化合物合成：用于肽和蛋白质放射性氟化的硫醇反应性合成。
影响因子：
1.6
作者：
Kiesewetter, Dale O.;Jacobson, Orit;Lang, Lixin;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan