Synthesis and preclinical evaluation of an Al(18)F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand.
Synthesis and preclinical evaluation of an Al(18)F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand.
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DOI：
10.1007/s00259-016-3437-y
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发表时间：
2016-11
影响因子：
9.1
通讯作者：
Herrmann, Ken
中科院分区：
文献类型：
--
作者：
Boschi, Stefano;Lee, Jason T.;Beykan, Seval;Slavik, Roger;Wei, Liu;Spick, Claudio;Eberlein, Uta;Buck, Andreas K.;Lodi, Filippo;Cicoria, Gianfranco;Czernin, Johannes;Lassmann, Michael;Fanti, Stefano;Herrmann, Ken
本研究的目的是合成和临床前评价18F-PSMA正电子发射断层扫描（PET）示踪剂。前列腺特异性膜抗原（PSMA）的特异性，生物分布，并在健康和荷瘤小鼠的剂量测定。筛选了通过18F-AlF-络合标记18F-PSMA-11的几种条件，以研究反应温度、肽量、乙醇体积和反应时间的影响。合成优化后，在C57 BL 6小鼠中进行生物分布和剂量测定研究。为了证明PSMA特异性，在小鼠对侧胁腹植入PSMA阴性（PC 3）和PSMA阳性（LNCaP）肿瘤。进行静态和动态microPET/计算机断层扫描（CT）成像。定量标记产率可以达到> 97%的放射化学纯度。18F-PSMA-11摄取在PSMA-高LNCaP中比在PSMA-低PC 3肿瘤中高24倍以上（分别为18.4 ± 3.3%ID/g和0.795 ± 0.260%ID/g; p < 4.2e-5）。在最后一个成像时间点后，通过组织的离体γ计数器分析确认结果。据报告，肾脏的吸收剂量最高。200 MBq给药活性的最大有效剂量为1.72 mSv。18F-PSMA-11使用氟化铝直接标记螯合物连接的肽检测到具有高肿瘤-肝脏比率的PSMA表达肿瘤。肾脏是剂量限制性器官。即使采用最严格的剂量学计算，高达0.56 GBq的注入放射性也是可行的。
The aim of this study was to synthesize and preclinically evaluate an 18F-PSMA positron emission tomography (PET) tracer. Prostate-specific membrane antigen (PSMA) specificity, biodistribution, and dosimetry in healthy and tumor-bearing mice were determined. Several conditions for the labeling of 18F-PSMA-11 via 18F-AlF-complexation were screened to study the influence of reaction temperature, peptide amount, ethanol volume, and reaction time. After synthesis optimization, biodistribution and dosimetry studies were performed in C57BL6 mice. For proof of PSMA-specificity, mice were implanted with PSMA-negative (PC3) and PSMA-positive (LNCaP) tumors in contralateral flanks. Static and dynamic microPET/computed tomography (CT) imaging was performed. Quantitative labeling yields could be achieved with >97 % radiochemical purity. The 18F-PSMA-11 uptake was more than 24-fold higher in PSMA-high LNCaP than in PSMA-low PC3 tumors (18.4 ± 3.3 %ID/g and 0.795 ± 0.260 %ID/g, respectively; p < 4.2e-5). Results were confirmed by ex vivo gamma counter analysis of tissues after the last imaging time point. The highest absorbed dose was reported for the kidneys. The maximum effective dose for an administered activity of 200 MBq was 1.72 mSv. 18F-PSMA-11 using direct labeling of chelate-attached peptide with aluminum-fluoride detected PSMA-expressing tumors with high tumor-to-liver ratios. The kidneys were the dose-limiting organs. Even by applying the most stringent dosimetric calculations, injected activities of up to 0.56 GBq are feasible.
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影响因子：
3.1
作者：
Dietlein M;Kobe C;Kuhnert G;Stockter S;Fischer T;Schomäcker K;Schmidt M;Dietlein F;Zlatopolskiy BD;Krapf P;Richarz R;Neubauer S;Drzezga A;Neumaier B
通讯作者：
Neumaier B
DOI：
10.1158/1078-0432.ccr-11-1357
发表时间：
2011-12-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Chen Y;Pullambhatla M;Foss CA;Byun Y;Nimmagadda S;Senthamizhchelvan S;Sgouros G;Mease RC;Pomper MG
通讯作者：
Pomper MG
影响因子：
6.2
作者：
Fuchs, Adrian V.;Tse, Brian W. C.;Thurecht, Kristofer J.
通讯作者：
Thurecht, Kristofer J.
DOI：
10.1007/s00259-015-3078-6
发表时间：
2015-07-01
影响因子：
9.1
作者：
Ceci, Francesco;Uprimny, Christian;Virgolini, Irene J.
通讯作者：
Virgolini, Irene J.
影响因子：
23.4
作者：
Budaeus, Lars;Leyh-Bannurah, Sami-Ramzi;Rosenbaum, Clemens
通讯作者：
Rosenbaum, Clemens