(44)Sc-PSMA-617 for radiotheragnostics in tandem with (177)Lu-PSMA-617-preclinical investigations in comparison with (68)Ga-PSMA-11 and (68)Ga-PSMA-617.
(44)Sc-PSMA-617 for radiotheragnostics in tandem with (177)Lu-PSMA-617-preclinical investigations in comparison with (68)Ga-PSMA-11 and (68)Ga-PSMA-617.
复制标题
（44）SC-PSMA-617用于与（177）LU-PSMA-617-preclinical研究相比（68）GA-PSMA-11和（68）GA-PSMA-617的（177）LU-PSMA-617-序列研究。
DOI：
10.1186/s13550-017-0257-4
复制
发表时间：
2017-12
期刊：
影响因子：
3.2
通讯作者：
Müller C
中科院分区：
文献类型：
--
作者：
Umbricht CA;Benešová M;Schmid RM;Türler A;Schibli R;van der Meulen NP;Müller C
靶向前列腺特异性膜抗原(PSMA)对于前列腺癌的放射诊断特别有意义。放射性标记的PSMA-617是一种1，4，7，10-四氮杂环十二烷-N，N‘，N’‘，N“’‘-四乙酸(DOTA)功能化的PSMA配体，具有良好的动力学特性和高的肿瘤摄取率，使其能够在临床上成功地应用于PET成像(68Ga)和放射性核素治疗(177Lu)。在这项研究中，用回旋加速器产生的44Sc(T1/2 = 4.04h)标记PSMA-617，并在临床前研究其作为177Lu-PSMA-617的诊断匹配的用途。在PSI的研究回旋加速器上，通过辐照浓缩的44Ca靶，然后进行层析分离，产生了44Sc。44Sc-PSMA-617是在高温下的标准标记条件下制备的，放化纯度为97%，比活度高达10MBq/nmol。用PSMA阳性的PC-3 PIP和PSMA阴性的PC-3流感前列腺癌细胞对44Sc-PSMA-617进行了体外评价，并与177Lu和68Ga标记的Match以及68Ga-PSMA-11进行了比较。在这些实验中，它的体外性质与177Lu和68Ga标记的PSMA-617相似。此外，44Sc-PSMA-617与表达PSMA的PC-3PIP肿瘤细胞特异性结合，而未观察到与PC-3Flu细胞的非特异性结合。研究了放射性配体在PC-3PIP/Flu荷瘤小鼠体内的性质。44Sc-PSMA-617显示肿瘤高摄取，肾脏快速排泄。44Sc-PSMA-617的整体组织分布与177Lu-PSMA-617最为相似，而68Ga标记的配体，尤其是68Ga-PSMA-11，表现出不同的分布动力学。44Sc-PSMA-617能够在注射后不久清晰地显示PC-3 PIP肿瘤移植瘤，随着时间的推移，肿瘤与背景的对比度增加，而在PC-3流感肿瘤中没有观察到非特异性摄取。44Sc-PSMA-617的体外性质和体内动力学与177Lu-PSMA-617相似，而与68Ga-PSMA-617和68Ga-PSMA-11相似。由于44Sc的半衰期比68Ga长近四倍，集中生产44Sc-PSMA-617并将其运往卫星PET中心将是可行的。这些特点使44Sc-PSMA-617特别适合临床应用。本文的在线版本(doi：10.1186/s13550-0170257-4)包含补充材料，授权用户可以使用。
The targeting of the prostate-specific membrane antigen (PSMA) is of particular interest for radiotheragnostic purposes of prostate cancer. Radiolabeled PSMA-617, a 1,4,7,10-tetraazacyclododecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA)-functionalized PSMA ligand, revealed favorable kinetics with high tumor uptake, enabling its successful application for PET imaging (68Ga) and radionuclide therapy (177Lu) in the clinics. In this study, PSMA-617 was labeled with cyclotron-produced 44Sc (T 1/2 = 4.04 h) and investigated preclinically for its use as a diagnostic match to 177Lu-PSMA-617. 44Sc was produced at the research cyclotron at PSI by irradiation of enriched 44Ca targets, followed by chromatographic separation. 44Sc-PSMA-617 was prepared under standard labeling conditions at elevated temperature resulting in a radiochemical purity of >97% at a specific activity of up to 10 MBq/nmol. 44Sc-PSMA-617 was evaluated in vitro and compared to the 177Lu- and 68Ga-labeled match, as well as 68Ga-PSMA-11 using PSMA-positive PC-3 PIP and PSMA-negative PC-3 flu prostate cancer cells. In these experiments it revealed similar in vitro properties to that of 177Lu- and 68Ga-labeled PSMA-617. Moreover, 44Sc-PSMA-617 bound specifically to PSMA-expressing PC-3 PIP tumor cells, while unspecific binding to PC-3 flu cells was not observed. The radioligands were investigated with regard to their in vivo properties in PC-3 PIP/flu tumor-bearing mice. 44Sc-PSMA-617 showed high tumor uptake and a fast renal excretion. The overall tissue distribution of 44Sc-PSMA-617 resembled that of 177Lu-PSMA-617 most closely, while the 68Ga-labeled ligands, in particular 68Ga-PSMA-11, showed different distribution kinetics. 44Sc-PSMA-617 enabled distinct visualization of PC-3 PIP tumor xenografts shortly after injection, with increasing tumor-to-background contrast over time while unspecific uptake in the PC-3 flu tumors was not observed. The in vitro characteristics and in vivo kinetics of 44Sc-PSMA-617 were more similar to 177Lu-PSMA-617 than to 68Ga-PSMA-617 and 68Ga-PSMA-11. Due to the almost four-fold longer half-life of 44Sc as compared to 68Ga, a centralized production of 44Sc-PSMA-617 and transport to satellite PET centers would be feasible. These features make 44Sc-PSMA-617 particularly appealing for clinical application. The online version of this article (doi:10.1186/s13550-017-0257-4) contains supplementary material, which is available to authorized users.