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镓-NOTA-尿抑素片段用于感染的 PET 成像:从实验室到临床。

Ga-NOTA-ubiquicidin fragment for PET imaging of infection: From bench to bedside.

机构信息

Radiopharmaceuticals Division, Bhabha Atomic Research Centre (BARC), Mumbai 400085, India; Homi Bhabha National Institute, Anushaktinagar, Mumbai 400094, India.

Radiopharmaceuticals Division, Bhabha Atomic Research Centre (BARC), Mumbai 400085, India; Homi Bhabha National Institute, Anushaktinagar, Mumbai 400094, India.

出版信息

J Pharm Biomed Anal. 2018 Sep 10;159:245-251. doi: 10.1016/j.jpba.2018.06.064. Epub 2018 Jul 2.

Abstract

This study explores the possibility of formulation of a cold kit for fast and easy preparation of a PET radiopharmaceutical, Ga-NOTA-UBI (29-41) for clinical translation. In this study, Circular dichroism (CD) spectroscopy to study conformation of NOTA-UBI (29-41) and its comparison with conformation of UBI (29-41) was done. Pharmaceutical grade cold kits of NOTA-UBI (29-41) were formulated for radiolabeling with Ga and necessary quality control tests were carried out. Ga-NOTA-UBI (29-41) could be prepared in >90% radiochemical yield and radiochemical purity using cold kits of NOTA-UBI (29-41). In vitro and in vivo evaluation of Ga-NOTA-UBI (29-41) was done to demonstrate specificity of the agent for imaging infection. Kits were utilized for preparation of patient dose of Ga-NOTA-UBI (29-41). Simple instant thin layer chromatography (ITLC) method for estimating radiolabeling yield of Ga-NOTA-UBI (29-41) at hospital radiopharmacy was demonstrated. Clinical evaluation was done in patients with suspected infection. 148-185 MBq of Ga-NOTA-UBI (29-41) was injected intravenously in three patients. Ga-NOTA-UBI (29-41) uptake could clearly delineate infection foci from non target normal tissues. This is the first report on formulation of a cold kit of NOTA-UBI (29-41) for preparation of Ga labeled NOTA-UBI(29-41) at hospital radiopharmacy for infection imaging. Initial clinical evaluation reveal it to be a prospective agent for imaging infection.

摘要

这项研究探讨了为临床转化制备 Ga-NOTA-UBI(29-41)正电子发射断层扫描(PET)放射性药物而快速简便地制备冷制剂的可能性。在这项研究中,进行了圆二色性(CD)光谱研究以研究 NOTA-UBI(29-41)的构象,并将其与 UBI(29-41)的构象进行了比较。制备了 NOTA-UBI(29-41)的制药级冷制剂套件,并进行了放射性标记用 Ga 的必要质量控制测试。使用 NOTA-UBI(29-41)的冷制剂套件,可制备出 >90%的 Ga-NOTA-UBI(29-41)的放射性化学产率和放射化学纯度。进行了 Ga-NOTA-UBI(29-41)的体外和体内评估,以证明该试剂用于感染成像的特异性。利用试剂盒为 Ga-NOTA-UBI(29-41)的患者剂量进行了准备。证明了医院放射药房中用于估计 Ga-NOTA-UBI(29-41)放射性标记产率的即时薄层色谱法(ITLC)的简便方法。在疑似感染的患者中进行了临床评估。三名患者静脉内注射了 148-185 MBq 的 Ga-NOTA-UBI(29-41)。Ga-NOTA-UBI(29-41)的摄取可以清楚地区分感染病灶与非靶正常组织。这是首次在医院放射药房中制备 NOTA-UBI(29-41)冷制剂套件以制备 Ga 标记的 NOTA-UBI(29-41)用于感染成像的报告。初步临床评估表明,这是一种有前途的感染成像剂。

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