Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
ISSN: 2155-9899
Chien-Chung Hsia*, Chung-Hsin Yeh, Chun-Tang Chen and Cheng Liang Peng
Introduction: C-X-C motif chemokine receptor 4 (CXCR4) plays a prominent role in inflammation, atherosclerosis, and cancer biology. Therefore, CXCR4 represents a promising target for molecular imaging in cardiovascular diseases such as atherosclerosis and arterial wall injury.CXCR4 and its cognate ligand, stromal cell–derived factor 1α (SDF- 1α), induced monocyte recruitment to the injured endothelium and subsequent plaque formation is the crucial progression of atherosclerosis. CXCR4 was been proved to be intensively expressed on monocytes/macrophage. [68Ga]-APD, based on CXCR4 antagonists TIQ-15, had designed as a PET tracer for imaging atherosclerosis. The aim of this study was to evaluate the biological characteristics of [68Ga]-APD, and compared with [18F]-FDG, [18F]- NaF, and [68Ga]-Pentixafor.
Results: The specification and quality of APD was identified by Mass, NMR and HPLC. After being labeled with Ga-68 under acetate buffer (pH=5.5), radiochemical purity was over 90% and stable for more than 4 hours in 37°C human serum. After being injected from tail vein on apolipoprotein-E-deficient (ApoE-/-) atherosclerotic mice, hydrophilic [68Ga]-APD was quickly eliminate from the kidney and bladder and accumulate in the atherosclerotic aorta. The highest target/background ratio (TBR) on atherosclerotic sites were 17.68 ± 0.71 (n=3) on high-fat diet ApoE-/- mice for 12 weeks after [68Ga]-APD injection about 1 hour. However, the TBR of [68Ga]-Pentixafor was only 2.06 ± 0.67 (n=3) on the same mice model. Competitive study represented that CXCR4 antagonist AMD3465 could effectively block the uptake of [68Ga]-APD on the atherosclerotic site and CXCR4 expression organs. Comparing with [18F]-FDG and [18F]-NaF, [68Ga]-APD represented relatively better TBR and specificity on the imaging of atherosclerotic lesions.
Conclusion: In vivo evaluation of CXCR4 expression in ApoE-/- mice revealed the high TBR of [68Ga]-APD on the atherosclerotic aorta and better than [68Ga]-Pentixafor. These evidences represented its feasible as a surrogate marker for inflammatory atherosclerosis.
Published Date: 2022-07-07; Received Date: 2022-06-06