Al-Momani Ehab, Israel Ina, Samnick Samuel
Department of Nuclear Medicine, University of Würzburg, D-97080 Würzburg, Germany.
Department of Nuclear Medicine, University of Würzburg, D-97080 Würzburg, Germany.
Appl Radiat Isot. 2017 Dec;130:102-108. doi: 10.1016/j.apradiso.2017.09.003. Epub 2017 Sep 6.
Imaging prostate-specific membrane antigen (PSMA) using positron emission tomography (PET) has been presented so far as the most sensitive and specific with regard to prostate cancer detection, in particular in high-risk prostate cancer patients. Currently, it mainly features Gallium-68 (Ga) labeled PSMA ligands, notably [Ga]Glu-urea-Lys(Ahx)-HBED-CC ([Ga]-PSMA-11) and [Ga]DOTAGA-FFK (Sub-KuE termed ([Ga]PSMA-I&T). However, Ga has several shortcomings as radionuclide including a short half-life and non-ideal energies. This has motivated consideration of F-labeled analogues for PET imaging of prostate cancer. Here, we describe a simple synthesis and validation of a fluorine-18 labeled Glu-urea-Lys(Ahx)-HBED-CC ([AlF]PSMA-11) for nuclear medicine applications. An efficient method for preparation of [AlF]PSMA-11 was developed and validated (according to Pharm Eur) for routinely clinical applications. [AlF]PSMA-11 was reproducibly obtained in radiochemical yields of 84 ± 6% (n = 15) and > 98% radiochemical purity using an improved one-step radiofluorination in aqueous solution. The total (production/preparation) time, including purification, pharmacological formulation of the isolated product and the quality control of the injectable solution was less than 60min. The [AlF]PSMA-11 was stable over 4h in 1% EtOH/saline selected as injection solution. The solution was sterile, non-pyrogenic and ready for clinical applications after sterile filtration through a 0.22µm membrane filter under sterile conditions. In addition, [AlF]PSMA-11 exhibited higher uptake and retention in PMSA-expressing LNCap prostate cells as compared to its clinically established Ga-labeled analogues [Ga]PSMA-11 and [Ga]PSMA-I&T as well as to [Ga]NOTA-Bn-PSMA. The simple and fast preparation of [AlF]PSMA-11 combined with its favorable pharmacological properties warrant its translation to a clinical setting.
The facile and high-yielding radiosynthesis of [AlF]PSMA-11as well as its promising in vitro and in-vivo characteristics makes it worthy of clinical development for PET imaging of prostate cancer.
迄今为止，使用正电子发射断层扫描（PET）对前列腺特异性膜抗原（PSMA）进行成像在前列腺癌检测方面表现出最高的敏感性和特异性，特别是在高危前列腺癌患者中。目前，它主要以镓 - 68（Ga）标记的PSMA配体为特征，尤其是[Ga]Glu - urea - Lys（Ahx）- HBED - CC（[Ga] - PSMA - 11）和[Ga]DOTAGA - FFK（Sub - KuE，称为[Ga]PSMA - I&T）。然而，Ga作为放射性核素存在几个缺点，包括半衰期短和能量不理想。这促使人们考虑用于前列腺癌PET成像的氟标记类似物。在此，我们描述了一种用于核医学应用的氟 - 18标记的Glu - urea - Lys（Ahx）- HBED - CC（[AlF]PSMA - 11）的简单合成及验证方法。开发并验证了一种制备[AlF]PSMA - 11的有效方法（根据欧洲药典）用于常规临床应用。使用改进的水溶液一步放射性氟化法，可重复获得放射化学产率为84±6%（n = 15）且放射化学纯度>98%的[AlF]PSMA - 11。包括纯化、分离产物的药物制剂和注射溶液的质量控制在内的总（生产/制备）时间少于60分钟。在选为注射溶液的1%乙醇/盐水中，[AlF]PSMA - 11在4小时内稳定。该溶液无菌、无热原，在无菌条件下通过0.22μm膜过滤器无菌过滤后即可用于临床应用。此外，与临床常用的Ga标记类似物[Ga]PSMA - 11、[Ga]PSMA - I&T以及[Ga]NOTA - Bn - PSMA相比，[AlF]PSMA - 11在表达PMSA的LNCap前列腺细胞中表现出更高的摄取和滞留。[AlF]PSMA - 11的简单快速制备及其良好的药理学特性使其有望转化为临床应用。
[AlF]PSMA - 11简便且高产率的放射性合成及其有前景的体外和体内特性使其值得用于前列腺癌PET成像的临床开发。
