当前位置：
X-MOL 学术
›
Bioconjugate Chem.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Improving the Imaging Contrast of 68Ga-PSMA-11 by Targeted Linker Design: Charged Spacer Moieties Enhance the Pharmacokinetic Properties
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2017-08-24 00:00:00 , DOI: 10.1021/acs.bioconjchem.7b00458 Ann-Christin Baranski , Martin Schäfer , Ulrike Bauder-Wüst , Anja Wacker , Jana Schmidt , Christos Liolios , Walter Mier 1 , Uwe Haberkorn 1 , Michael Eisenhut , Klaus Kopka , Matthias Eder 2
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2017-08-24 00:00:00 , DOI: 10.1021/acs.bioconjchem.7b00458 Ann-Christin Baranski , Martin Schäfer , Ulrike Bauder-Wüst , Anja Wacker , Jana Schmidt , Christos Liolios , Walter Mier 1 , Uwe Haberkorn 1 , Michael Eisenhut , Klaus Kopka , Matthias Eder 2
Affiliation
|
68Ga-Glu-urea-Lys-(Ahx)-HBED-CC (68Ga-PSMA-11) represents a successful radiopharmaceutical for PET/CT imaging of prostate cancer. Further optimization of the tumor-to-background contrast might significantly enhance the sensitivity of PET/CT imaging and the probability of detecting recurrent prostate cancer at low PSA values. This study describes the advantage of histidine (H)/glutamic acid (E) and tryptophan (W)/glutamic acid (E) containing linkers on the pharmacokinetic properties of 68Ga-PSMA-11. The tracers were obtained by a combination of standard Fmoc-based solid-phase synthesis and copper(I)-catalyzed azide–alkyne cycloaddition. Their 68Ga complexes were compared to the clinical reference 68Ga-PSMA-11 with respect to cell binding, effective internalization, and tumor targeting properties in LNCaP-bearing balb/c nu/nu mice. The introduction of (HE)i (i = 1–3) or (WE)i (i = 1–3) into PSMA-11 resulted in a significantly changed biodistribution profile. The uptake values in kidneys, spleen, liver, and other background organs were reduced for (HE)3 while the tumor uptake was not affected. For (HE)1 the tumor uptake was significantly increased. The introduction of tryptophan-containing linkers also modulated the organ distribution profile. The results clearly indicate that histidine is of essential impact in order to improve the tumor-to-organ contrast. Hence, the histidine/glutamic acid linker modifications considerably improved the pharmacokinetic properties of 68Ga-PSMA-11 leading to a reduced uptake in dose limiting organs and a significantly enhanced tumor-to-background contrast. Glu-urea-Lys-(HE)3-HBED-CC represents a promising 68Ga complex ligand for PET/CT-imaging of prostate cancer.
中文翻译：
通过有针对性的接头设计改善68 Ga-PSMA-11的成像对比度：带电间隔基部分增强了药代动力学特性
68 Ga-Glu-脲-Lys-（Ahx）-HBED-CC（68 Ga-PSMA-11）代表前列腺癌PET / CT成像的成功放射性药物。肿瘤与背景对比的进一步优化可能会显着提高PET / CT成像的敏感性，并在低PSA值下检测出复发性前列腺癌的可能性。这项研究描述了组氨酸（H）/谷氨酸（E）和色氨酸（W）/谷氨酸（E）含接头对68 Ga-PSMA-11药代动力学特性的优势。示踪剂是通过基于标准Fmoc的固相合成和铜（I）催化的叠氮化物-炔烃环加成反应获得的。将他们的68 Ga复合物与临床参考文献68进行了比较Ga-PSMA-11在携带LNCaP的balb / c nu / nu小鼠中的细胞结合，有效内在化和肿瘤靶向特性方面。在PSMA-11中引入（HE）i（i = 1-3）或（WE）i（i = 1-3）导致生物分布特征发生了显着变化。（HE）3降低了肾脏，脾脏，肝脏和其他背景器官的摄取值，而不会影响肿瘤的摄取。对于（HE）1肿瘤吸收显着增加。含有色氨酸的接头的引入也调节了器官分布特征。结果清楚地表明，组氨酸对于改善肿瘤与器官的对比具有至关重要的作用。因此，组氨酸/谷氨酸接头修饰大大改善了68 Ga-PSMA-11的药代动力学特性，导致剂量限制器官的摄取减少和肿瘤与背景的对比显着增强。Glu-urea-Lys-（HE）3 -HBED-CC代表有前途的68 Ga复合物配体，可用于前列腺癌的PET / CT成像。
更新日期：2017-08-24
中文翻译：
通过有针对性的接头设计改善68 Ga-PSMA-11的成像对比度：带电间隔基部分增强了药代动力学特性
68 Ga-Glu-脲-Lys-（Ahx）-HBED-CC（68 Ga-PSMA-11）代表前列腺癌PET / CT成像的成功放射性药物。肿瘤与背景对比的进一步优化可能会显着提高PET / CT成像的敏感性，并在低PSA值下检测出复发性前列腺癌的可能性。这项研究描述了组氨酸（H）/谷氨酸（E）和色氨酸（W）/谷氨酸（E）含接头对68 Ga-PSMA-11药代动力学特性的优势。示踪剂是通过基于标准Fmoc的固相合成和铜（I）催化的叠氮化物-炔烃环加成反应获得的。将他们的68 Ga复合物与临床参考文献68进行了比较Ga-PSMA-11在携带LNCaP的balb / c nu / nu小鼠中的细胞结合，有效内在化和肿瘤靶向特性方面。在PSMA-11中引入（HE）i（i = 1-3）或（WE）i（i = 1-3）导致生物分布特征发生了显着变化。（HE）3降低了肾脏，脾脏，肝脏和其他背景器官的摄取值，而不会影响肿瘤的摄取。对于（HE）1肿瘤吸收显着增加。含有色氨酸的接头的引入也调节了器官分布特征。结果清楚地表明，组氨酸对于改善肿瘤与器官的对比具有至关重要的作用。因此，组氨酸/谷氨酸接头修饰大大改善了68 Ga-PSMA-11的药代动力学特性，导致剂量限制器官的摄取减少和肿瘤与背景的对比显着增强。Glu-urea-Lys-（HE）3 -HBED-CC代表有前途的68 Ga复合物配体，可用于前列腺癌的PET / CT成像。
京公网安备 11010802027423号