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三种用于胆囊收缩素受体成像的 68Ga-和 111In 标记肽的体外和体内特性。

In vitro and in vivo characterization of three 68Ga- and 111In-labeled peptides for cholecystokinin receptor imaging.

机构信息

Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.

出版信息

Mol Imaging. 2012 Sep-Oct;11(5):401-7.

Abstract

Cholecystokinin (CCK) receptors are overexpressed in several human tumor types, such as medullary thyroid carcinomas and small cell lung cancers. Several ligands for the CCK2 receptor (CCK2R) have been developed for radionuclide targeting of these tumors. In this study, we evaluated whether radiolabeled DOTA-sCCK8 and its stabilized derivative, DOTA-sCCK8[Phe(2)(p-CH2SO3H), Nle(3,6)], are suitable for imaging of CCK2R-positive tumors, using DOTA-MG0 as a reference. In vivo targeting of CCK2R-positive tumors with DOTA-sCCK8, DOTA-sCCK8[Phe(2)(p-CH2SO3H), Nle(3,6)], and DOTA-MG0, labeled with (111)In or (68)Ga, was evaluated in BALB/c nude mice with a subcutaneous A431-CCK2R tumor. Biodistribution studies and single-photon emission computed tomography (SPECT) and positron emission tomography (PET) were performed at 1 hour postinjection. All peptides specifically accreted in the CCK2R-expressing tumors. Both (111)In-DOTA-sCCK8 and (111)In-DOTA-sCCK8[Phe(2)(p-CH2SO3H), Nle(3,6)] showed good tumor retention (4.65% ID/g and 5.44% ID/g, respectively, at 4 hours postinjection). On PET/computed tomographic (CT) and SPECT/CT scans, subcutaneous A431-CCK2R tumors were clearly visualized with low uptake of sCCK8 peptides in the intestines. Whereas radiolabeled DOTA-MG0 showed high kidney uptake (70% ID/g), the sCCK8 peptides showed low uptake in the kidneys. Sulfated CCK8 analogues combined high tumor uptake with low retention in the kidney and are therefore promising tracers for imaging of CCK2R-positive tumors.

摘要

胆囊收缩素(CCK)受体在多种人类肿瘤类型中过表达,例如髓样甲状腺癌和小细胞肺癌。已经开发了几种 CCK2 受体(CCK2R)的配体,用于这些肿瘤的放射性核素靶向。在这项研究中,我们评估了放射性标记的 DOTA-sCCK8 及其稳定衍生物 DOTA-sCCK8[Phe(2)(p-CH2SO3H), Nle(3,6)]是否适合用于成像 CCK2R 阳性肿瘤,DOTA-MG0 用作参比。用(111)In 或(68)Ga 标记 DOTA-sCCK8、DOTA-sCCK8[Phe(2)(p-CH2SO3H), Nle(3,6)]和 DOTA-MG0,在皮下 A431-CCK2R 肿瘤的 BALB/c 裸鼠中评估其对 CCK2R 阳性肿瘤的靶向作用。在注射后 1 小时进行生物分布研究和单光子发射计算机断层扫描(SPECT)和正电子发射断层扫描(PET)。所有肽都特异性地在 CCK2R 表达的肿瘤中积累。(111)In-DOTA-sCCK8 和(111)In-DOTA-sCCK8[Phe(2)(p-CH2SO3H), Nle(3,6)]均显示出良好的肿瘤保留(分别为 4 小时后注射时的 4.65% ID/g 和 5.44% ID/g)。在 PET/CT 和 SPECT/CT 扫描中,皮下 A431-CCK2R 肿瘤可清晰显示,肠内 sCCK8 肽摄取量低。而放射性标记的 DOTA-MG0 显示出高肾摄取(70% ID/g),sCCK8 肽在肾脏中的摄取量低。硫酸化 CCK8 类似物结合了高肿瘤摄取和低肾脏保留,因此是用于成像 CCK2R 阳性肿瘤的有前途的示踪剂。

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