Gold nanoparticles-based SPECT/CT imaging probe targeting for vulnerable atherosclerosis plaques.

In order to realize accurate localization and precise evaluation of vulnerability of atherosclerotic plaques via dual-modal imaging, gold nanoparticles (GNPs) were firstly caped with a thin amino-PEGs cover and then conjugated with the targeting molecular Annexin V and radionuclide Tc-99m simultaneously to form SPECT/CT imaging probe targeting apoptotic macrophages. The as-synthesized (99m)Tc-GNPs-Annexin V was with uniform size (30.2 ± 2.9 nm) and high labeling rate (98.9 ± 0.5%) and stability. Targeting ability of Annexin V for apoptotic macrophages was kept and enhanced. For macrophages with 30% apoptosis, cellular uptakes of 3.52 ± 0.35% for (99m)Tc-GNPs-Annexin V, 2.41 ± 0.53% for (99m)Tc-GNPs and 1.68 ± 0.36% for (99m)Tc-Annexin V were achieved after 2 h incubation. ApoE knock out mice with high fat diet-induced atherosclerosis were scanned via (99m)Tc-GNPs-Annexin V SPECT/CT. With the introduction of targeting molecules, imaging probe was more efficient in accumulating in apoptotic macrophages. In practical evaluation, CT helps to restrict the lesions depiction more accurately, meanwhile, SPECT imaging intensity correlated with pathological changes tightly. In conclusion, Annexin V-modified hybrid gold nanoparticles were successfully synthesized, and this imaging system helped to better localize and diagnose those vulnerable AS plaques via specific targeting the apoptotic macrophages.

[1]  K. Ogawa,et al.  Development and Evaluation of a Novel 99mTc-Labeled Annexin A5 for Early Detection of Response to Chemotherapy , 2013, PloS one.

[2]  Qinghua Zhao,et al.  Noninvasive detection of macrophages in atherosclerotic lesions by computed tomography enhanced with PEGylated gold nanoparticles , 2014, International journal of nanomedicine.

[3]  S. Logothetidis,et al.  Nanomedicine for Atherosclerosis: Molecular Imaging and Treatment. , 2015, Journal of biomedical nanotechnology.

[4]  M. Nahrendorf,et al.  Multimodal iron oxide nanoparticles for hybrid biomedical imaging , 2013, NMR in biomedicine.

[5]  R. Virmani,et al.  Broad and specific caspase inhibitor-induced acute repression of apoptosis in atherosclerotic lesions evaluated by radiolabeled annexin A5 imaging. , 2007, Journal of the American College of Cardiology.

[6]  Xinrong Liu,et al.  An improved synthesis of NHS-MAG3 for conjugation and radiolabeling of biomolecules with 99mTc at room temperature , 2007, Nature Protocols.

[7]  S. Hammad,et al.  Accelerated vascular disease in systemic lupus erythematosus: role of macrophage. , 2015, Clinical immunology.

[8]  Na Li,et al.  FRET-based nanoprobes for simultaneous monitoring of multiple mRNAs in living cells using single wavelength excitation. , 2016, Chemical communications.

[9]  E. Edelman,et al.  Coronary artery disease and diabetes mellitus. , 2014, Cardiology clinics.

[10]  M. Wong,et al.  Rapid emergence of atherosclerosis in Asia: a systematic review of coronary atherosclerotic heart disease epidemiology and implications for prevention and control strategies , 2015, Current opinion in lipidology.

[11]  C. L. Teoh,et al.  New Targets of Molecular Imaging in Atherosclerosis: Prehension of Current Status , 2015, Analytical sciences : the international journal of the Japan Society for Analytical Chemistry.

[12]  Shiyuan Liu,et al.  Tumor Angiogenesis Targeted Radiosensitization Therapy Using Gold Nanoprobes Guided by MRI/SPECT Imaging. , 2016, ACS applied materials & interfaces.

[13]  Kwangmeyung Kim,et al.  Hyaluronic acid nanoparticles for active targeting atherosclerosis. , 2015, Biomaterials.

[14]  M. Hu,et al.  Measurement of protein thiol groups and glutathione in plasma. , 1994, Methods in enzymology.

[15]  J. Egido,et al.  Targeted gold-coated iron oxide nanoparticles for CD163 detection in atherosclerosis by MRI , 2015, Scientific Reports.

[16]  Han Liu,et al.  Dual molecular imaging for targeting metalloproteinase activity and apoptosis in atherosclerosis: molecular imaging facilitates understanding of pathogenesis , 2009, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[17]  Na Li,et al.  A multicolor nanoprobe for detection and imaging of tumor-related mRNAs in living cells. , 2012, Angewandte Chemie.

[18]  K. Ley,et al.  Beyond vascular inflammation—recent advances in understanding atherosclerosis , 2015, Cellular and Molecular Life Sciences.

[19]  F. Blankenberg,et al.  99mTc-Annexin A5 quantification of apoptotic tumor response: a systematic review and meta-analysis of clinical imaging trials , 2015, European Journal of Nuclear Medicine and Molecular Imaging.

[20]  J. Tardif,et al.  Novel anti-inflammatory therapies for the treatment of atherosclerosis. , 2015, Atherosclerosis.

[21]  Na Li,et al.  Multiplexed detection and imaging of intracellular mRNAs using a four-color nanoprobe. , 2013, Analytical chemistry.

[22]  Da Xing,et al.  Gadolinium(III)-gold nanorods for MRI and photoacoustic imaging dual-modality detection of macrophages in atherosclerotic inflammation. , 2013, Nanomedicine.

[23]  D. Harrison,et al.  Macrophages in vascular inflammation – From atherosclerosis to vasculitis , 2015, Autoimmunity.

[24]  Na Li,et al.  Dual-targeted nanocarrier based on cell surface receptor and intracellular mRNA: an effective strategy for cancer cell imaging and therapy. , 2013, Analytical chemistry.

[25]  J. Michel,et al.  Preclinical Validation of 99mTc–Annexin A5–128 in Experimental Autoimmune Myocarditis and Infective Endocarditis: Comparison with 99mTc–HYNIC–Annexin A5 , 2015, Molecular imaging.

[26]  Simultaneous Visualization of Multiple mRNAs and Matrix Metalloproteinases in Living Cells Using a Fluorescence Nanoprobe. , 2015, Chemistry.

[27]  Ning Su,et al.  Iodine-125-labeled cRGD-gold nanoparticles as tumor-targeted radiosensitizer and imaging agent , 2015, Nanoscale Research Letters.

[28]  J. Alpert,et al.  The epidemic of the 20(th) century: coronary heart disease. , 2014, The American journal of medicine.

[29]  M. Austin,et al.  Low-Density Lipoprotein Cholesterol, Apolipoprotein B, and Risk of Coronary Heart Disease , 2013, Biological research for nursing.

[30]  Hongcheng Shi,et al.  Detection of vulnerable atherosclerosis plaques with a dual-modal single-photon-emission computed tomography/magnetic resonance imaging probe targeting apoptotic macrophages. , 2015, ACS applied materials & interfaces.

[31]  J. Boer,et al.  A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease , 2014, Atherosclerosis.

[32]  C. Lavie,et al.  The impact of obesity on risk factors and prevalence and prognosis of coronary heart disease-the obesity paradox. , 2014, Progress in cardiovascular diseases.

[33]  Peter Chhour,et al.  Labeling monocytes with gold nanoparticles to track their recruitment in atherosclerosis with computed tomography. , 2016, Biomaterials.