Subjects: Biology >> Biophysics submitted time 2016-05-05
Li, Dan
Chen, Yuanyuan
Wang, Xia
Chen, Xin
Liu, Boli
Jia, Hongmei
Deuther-Conrad, Winnie
Steinbach, Joerg
Brust, Peter
Jia, Bing
Dong, Chengyan
Abstract： We have designed and synthesized a series of cyclopentadienyl tricarbonyl rhenium complexes containing a 5,6-dimethoxyisoindoline or a 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline pharmacophore as sigma(2) receptor ligands. Rhenium compound 20a possessed low nanomolar sigma(2) receptor affinity (K-i = 2.97 nM) and moderate subtype selectivity (10-fold). Moreover, it showed high selectivity toward vesicular acetylcholine transporter (2374-fold), dopamine D-2L receptor, NMDA receptor, opiate receptor, dopamine transporter, norepinephrine transporter, and serotonin transporter. Its corresponding radiotracer [Tc-99m]20b showed high uptake in a time- and dose-dependent manner in DU145 prostate cells and C6 glioma cells. In addition, this tracer exhibited high tumor uptake (5.92% ID/g at 240 min) and high tumor/blood and tumor/muscle ratios (21 and 16 at 240 min, respectively) as well as specific binding to sigma receptors in nude mice bearing C6 glioma xenografts. Small animal SPECT/CT imaging of [Tc-99m]20b in the C6 glioma xenograft model demonstrated a clear visualization of the tumor at 180 min after injection.
Peer Review Status:
Awaiting Review
Subjects: Biology >> Biophysics submitted time 2016-05-05
Dong, Chengyan
Yang, Sujuan
Zhao, Huiyun
Liu, Zhaofei
Jia, Bing
Wang, Fan
Dong, Chengyan
Yang, Sujuan
Zhao, Huiyun
Liu, Zhaofei
Jia, Bing
Wang, Fan
Dong, Chengyan
Shi, Jiyun
Wang, Fan
Zhao, Huiyun
Zhong, Lijun
Wang, Fan
Abstract： We describe herein dual-modality imaging of intraperitoneal colon tumor using an avidin/biotin pretargeting system. A novel dual-modality probe,Tc-99m-HYNIC-lys(Cy5.5)-PEG4-biotin,was designed, synthesized and characterized. Single-photon emission computed tomography/computed tomography (SPECT/CT) imaging and near infrared fluorescence (NIRF) imaging were developed using intraperitoneal LS180 human colon adenocarcinoma xenografts. Following avidin preinjection for 4 hours, 99mTc-HYNIC-lys(Cy5.5)-PEG4-biotin could successfully detect colon tumors of different sizes inside the abdominal region using both modalities, and the imaging results showed no differences. Biodistribution studies demonstrated that the tumors had a very high uptake of the probe (TcHYNIC)-Tc-99m-lys(Cy5.5)-PEG4-biotin(12.74 +/- 1.89% ID/g at 2 h p.i.), and the clearance from blood and other normal tissues occured very fast. The low tumor uptake in the non-pretargeted mice (1.63 +/- 0.50% ID/g at 2 h p.i.) and tumor cell staining results showed excellent tumor binding specificity of the pretargeting system. The ability of the novel probe to show excellent imaging quality with high tumor-to-background contrast, a high degree of binding specificity with tumors and excellent in vivo biodistribution pharmacokinetics should prove that the avidin/biotin based dual-modality pretargeting probe is a promising imaging tool during the entire period of tumor diagnosis and treatment.
Peer Review Status:Awaiting Review
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