Acta Chimica Sinica ›› 2014, Vol. 72 ›› Issue (4): 427-432.DOI: 10.6023/A13121248 Previous Articles     Next Articles



朱华a, 李囡a, 林新峰a, 洪业b, 杨志a   

  1. a 北京大学肿瘤医院暨北京市肿瘤防治研究所 核医学科 恶性肿瘤发病机制及转化研究教育部重点实验室 100142;
    b 中国原子能科学研究院同位素所 北京275信箱 102413
  • 投稿日期:2013-12-12 发布日期:2014-01-08
  • 通讯作者: 杨志; Tel.:0086-010-88196192
  • 基金资助:

Design and Synthesis of 111In-CCPM-RGD Nanoparticles for Dual-modality Molecular Imaging

Zhu Huaa, Li Nana, Lin Xinfenga, Hong Yeb, Yang Zhia   

  1. a Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142;
    b Isotope Department, China Institute of Atomic Energy, Beijing 102413
  • Received:2013-12-12 Published:2014-01-08
  • Supported by:
    Project supported by the National Natural Science Foundation of China (Nos. 81071198, 81172082, 81371592) and Beijing Natural Science Foundation (No. 7132040).

The multi-modality probes are essential for multi-modality imaging. Dual labeled imaging probes allow the same target to be evaluated with two different modalities. Based on the structure of c-RGD peptide motif, some examples of multimodality agents have been reported in design of RGD for αvβ3 intergin positive tumor imaging. The aim of this study was to develop a dual-labeled nanoparticles for both single photon emission computed tomography (SPECT) and near-infrared fluorescence (NIRF) imaging of αvβ3. In this paper, c-RGD was conjugated to near-infrared fluorescence fluorophores (Cy7) entrapped polyethylene glycol-coated, core-crosslinked polymeric micelles (NIRF-CCPM) labeled with a radioisotope indium 111. The labeling efficiency was over 96%, the radio chemical purity was over 99% after purification. The in vitro stability tests were presented in 5% bull serum albumin (BSA) for 72 h at 25 ℃. Less than 10% 111In dissociation was detected by Radio-Thin-Layer Chromatography. 111In-CCPM-RGD seems to be a promising candidate for dual optical and nuclear imaging applications in tumor detection. Its structure was fully characterized. Serial SPECT imaging of human glioma U87 tumor-bearing nude mice revealed that tumor uptake of 111In-CCPM-RGD got a substantial growth from 24 h to 72 h after post-injection of 11.1 MBq nanoparticles, corroborated by in vivo NIRF imaging. Tumor uptake as measured by in vivo NIRF imaging by region of interest (ROI) with the unit of average radiant efficiency. The ROI of tumor NIRF imaging were 4.81×107 and 6.91×107 [p/sec/cm2/sr]/[μW/cm2] at 24 h, 72 h respectively. The in vivo SPECT imaging was general concordance with NIRF imaging. The combination of these nuclear and NIRF imaging technologies will significantly improve the accuracy in tumor diagnosis. The persistent, excellent, and αvβ3-specific uptake of 111In-CCPM-RGD in the tumor, observed by both SPECT and NIRF imaging, warrants further investigation and future clinical translation of such nanoparticles-based imaging agents.

Key words: core-crosslinked polymeric micelles, tumor target, dual-modality imaging, indium-111