■用于成像多巴胺转运蛋白的新型放射性示踪剂开发是一个令人感兴趣的主题,因为尽管[99mTc]TRODAT-1,[123I]β-CIT,和[123I]FP-CIT可商购获得;99Mo/99mTc发电机供不应求,123I的生产高度依赖于紧凑型回旋加速器。因此,我们设计了一种基于托烷衍生物的新型正电子发射断层扫描(PET)示踪剂,通过C-2修饰共轭NOTA来螯合68Ga,衍生自68Ge/68Ga发生器的放射性同位素。
■在室温下合成IPCAT-NOTA22并用[68Ga]GaCl4-标记。血清稳定性的生物学研究,LogP,并进行了体外放射自显影(结合测定和竞争测定)。此外,离体放射自显影,生物分布,在SpragueDawley大鼠中进行动态PET成像研究。
■获得的[68Ga]IPCAT-NOTA24具有≥90%的放射化学产率和4.25MBq/nmol的比活性。85%放射化学纯度(RCP%)的[68Ga]IPCAT-NOTA24在血清中在37°C下稳定长达60分钟,亲脂性为0.88。60分钟时特异性结合率(SBR%)达到15.8±6.7,在体外结合研究中,通过共注射冷前体的100倍和1000倍,可以阻断85%的特异性摄取。[68Ga]IPCAT-NOTA24大鼠的组织区域分布研究显示纹状体摄取(5分钟时为0.02%,60分钟时为0.007%),SBR%为6%,25%,在5-15、30-40和60-70分钟时占62%,分别,在NanoPET研究中。体内30分钟时[68Ga]IPCAT-NOTA24的RCP%保持为67.65%。
■此处描述的数据提供了有关用于DAT成像的缀合/悬垂方法的PET探针设计的新信息。必须使用另一种螯合剂或另一种直接的颅内注射方法来证明[68Ga]IPCAT-NOTA24摄取与转运蛋白定位之间的关系。
UNASSIGNED: Novel radiotracer development for imaging dopamine transporters is a subject of interest because although [99mTc]TRODAT-1, [123I]β-CIT, and [123I]FP-CIT are commercially available; 99Mo/99mTc generator is in short supply and 123I production is highly dependent on compact cyclotron. Therefore, we designed a novel positron emission tomography (PET) tracer based on a tropane derivative through C-2 modification to conjugate NOTA for chelating 68Ga, a radioisotope derived from a 68Ge/68Ga generator.
UNASSIGNED: IPCAT-NOTA 22 was synthesized and labeled with [68Ga]GaCl4 - at room temperature. Biological studies on serum stability, LogP, and in vitro autoradiography (binding assay and competitive assay) were performed. Furthermore, ex vivo autoradiography, biodistribution, and dynamic PET imaging studies were performed in Sprague Dawley rats.
UNASSIGNED: [68Ga]IPCAT-NOTA 24 obtained had a radiochemical yield of ≥90% and a specific activity of 4.25 MBq/nmol. [68Ga]IPCAT-NOTA 24 of 85% radiochemical purity (RCP%) was stable at 37°C for up to 60 minutes in serum with a lipophilicity of 0.88. The specific binding ratio (SBR%) reached 15.8 ± 6.7 at 60 minutes, and the 85% specific uptake could be blocked through co-injection at 100- and 1000-fold of the cold precursor in in vitro binding studies. Tissue regional distribution studies in rats with [68Ga]IPCAT-NOTA 24 showed striatal uptake (0.02% at 5 minutes and 0.007% at 60 minutes) with SBR% of 6%, 25%, and 62% at 5-15, 30-40, and 60-70 minutes, respectively, in NanoPET studies. The RCP% of [68Ga]IPCAT-NOTA 24 at 30 minutes in vivo remained 67.65%.
UNASSIGNED: Data described here provide new information on the design of PET probe of conjugate/pendent approach for DAT imaging. Another chelator or another direct method of intracranial injection must be used to prove the relation between [68Ga]IPCAT-NOTA 24 uptake and transporter localization.