Development and preliminary application of novel radiotracers targeting CD36
10.3760/cma.j.cn321828-20250421-00113
- VernacularTitle:靶向CD36新型放射性示踪剂的研制及初步应用
- Author:
Bo ZHOU
1
;
Ting LIANG
1
;
Chao ZHANG
1
;
Feng GAO
1
Author Information
1. 山东大学基础医学院实验核医学研究中心，济南 250012
- Publication Type:Journal Article
- Keywords:
Glioblastoma;
Antigens, CD36;
Isotope labeling;
Gallium radioisotopes;
Positron-emission tomography;
Tumor cells, cultured;
Mice
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2025;45(8):464-469
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To construct novel radiotracers targeting CD36 and evaluate their stabilities and targeting specificities.Methods:ABT-510, an anti-angiogenic peptide that bound CD36, served as the active scaffold for the synthesis of precursor molecules BQ01, BQ02 and BQ03. These precursors were subsequently labeled with 68Ga to yield the tracers 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03, whose radiochemical purities were determined by radio-high-performance liquid chromatography. A systematic characteristics of the radiochemical and biological profiles were performed, including in vitro stability, lipid water partition coefficient (log P), target-binding affinity, pharmacokinetic behaviour, microPET/CT imaging on U87MG tumor bearing mice, biodistribution, and phosphor-screen autoradiography. The tumor/muscle ratios of three probes were compared by one-way analysis of variance (post-hoc tests with Tukey method). Results:The radiochemical purities of 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 were all over 95%, and the radiotracers all remained stable in PBS and serum in vitro. The log P values of 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 were -3.81±0.08, -3.60±0.03 and -3.85±0.03 respectively, indicating hydrophilicity; and blood clearance half-lives in vivo were (25.6±0.3), (38.2±0.2) and (17.5±0.2) min respectively, demonstrating rapid elimination. 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 displayed high binding affinities toward U87MG cells, with inhibition constants ( Ki) of (4.30±0.63), (3.80±0.24) and (2.61±0.31)nmol/L, respectively. MicroPET/CT demonstrated marked tumor accumulation of 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 at 0.5 h after administration in U87MG tumor bearing mice, with SUV max of 0.68±0.09, 0.70±0.09 and 0.89±0.05. Biodistribution results showed the tumor uptakes of 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 were (0.35±0.09), (0.53±0.01) and (0.63±0.06) percentage activity of injection dose per gram of tissue (%ID/g), respectively. The tumor/muscle ratio of 68Ga-BQ03 was significantly higher than that of 68Ga-BQ01 or 68Ga-BQ02 ( F=161.50, all P<0.001). Conclusions:Three CD36-targeted radiotracers demonstrate good stability, strong binding affinity, and high tumor uptake. Among them, 68Ga-BQ03 shows the best imaging performance and holds promise for the precise diagnosis of CD36-positive malignant tumors.
