Nanoparticle PET-CT Imaging of Macrophages in Inflammatory Atherosclerosis Export

@article{citeulike:2414576, abstract = {Background Macrophages participate centrally in atherosclerosis, and macrophage markers (eg, CD68, MAC-3) correlate well with lesion severity and therapeutic modulation. On the basis of the avidity of lesional macrophages for polysaccharide-containing supramolecular structures such as nanoparticles, we have developed a new positron emission tomography (PET) agent with optimized pharmacokinetics to allow in vivo imaging at tracer concentrations. Methods and Results A dextranated and DTPA-modified magnetofluorescent 20-nm nanoparticle was labeled with the PET tracer 64Cu (1 mCi/0.1 mg nanoparticles) to yield a PET, magnetic resonance, and optically detectable imaging agent. Peak PET activity 24 hours after intravenous injection into mice deficient in apolipoprotein E with experimental atherosclerosis mapped to areas of high plaque load identified by computed tomography such as the aortic root and arch and correlated with magnetic resonance and optical imaging. Accumulated dose in apolipoprotein Edeficient aortas determined by gamma counting was 260\% and in carotids 392\% of respective wild-type organs (P<0.05 both). Autoradiography of aortas demonstrated uptake of the agent into macrophage-rich atheromata identified by Oil Red O staining of lipid deposits. The novel nanoagent accumulated predominantly in macrophages as determined by fluorescence microscopy and flow cytometry of cells dissociated from aortas. Conclusions This report establishes the capability of a novel trimodality nanoparticle to directly detect macrophages in atherosclerotic plaques. Advantages include improved sensitivity; direct correlation of PET signal with an established biomarker (CD68); ability to readily quantify the PET signal, perform whole-body vascular surveys, and spatially localize and follow the trireporter by microscopy; and clinical translatability of the agent given similarities to magnetic resonance imaging probes in clinical trials. 10.1161/CIRCULATIONAHA.107.741181}, author = {Nahrendorf, Matthias and Zhang, Hanwen and Hembrador, Sheena and Panizzi, Peter and Sosnovik, David E. and Aikawa, Elena and Libby, Peter and Swirski, Filip K. and Weissleder, Ralph}, citeulike-article-id = {2414576}, citeulike-linkout-0 = {http://dx.doi.org/10.1161/CIRCULATIONAHA.107.741181}, citeulike-linkout-1 = {http://circ.ahajournals.org/cgi/content/abstract/117/3/379}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18158358}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18158358}, day = {22}, doi = {10.1161/CIRCULATIONAHA.107.741181}, journal = {Circulation}, keywords = {64cu-tnp, atherosclerosis, atherosclerotic-plaque, biodistribution, ccne-grant, dextran-coated-aminated-clio, flow-cytometry, macrophage, mit-mgh-ccne, multimodal-nanoparticle, pet-ct-imaging}, month = {January}, number = {3}, pages = {379--387}, posted-at = {2008-02-22 16:47:36}, priority = {0}, title = {Nanoparticle PET-CT Imaging of Macrophages in Inflammatory Atherosclerosis}, url = {http://dx.doi.org/10.1161/CIRCULATIONAHA.107.741181}, volume = {117}, year = {2008} }

TY - JOUR ID - citeulike:2414576 L3 - citeulike-article-id:2414576 N2 - Background Macrophages participate centrally in atherosclerosis, and macrophage markers (eg, CD68, MAC-3) correlate well with lesion severity and therapeutic modulation. On the basis of the avidity of lesional macrophages for polysaccharide-containing supramolecular structures such as nanoparticles, we have developed a new positron emission tomography (PET) agent with optimized pharmacokinetics to allow in vivo imaging at tracer concentrations. Methods and Results A dextranated and DTPA-modified magnetofluorescent 20-nm nanoparticle was labeled with the PET tracer 64Cu (1 mCi/0.1 mg nanoparticles) to yield a PET, magnetic resonance, and optically detectable imaging agent. Peak PET activity 24 hours after intravenous injection into mice deficient in apolipoprotein E with experimental atherosclerosis mapped to areas of high plaque load identified by computed tomography such as the aortic root and arch and correlated with magnetic resonance and optical imaging. Accumulated dose in apolipoprotein Edeficient aortas determined by gamma counting was 260% and in carotids 392% of respective wild-type organs (P<0.05 both). Autoradiography of aortas demonstrated uptake of the agent into macrophage-rich atheromata identified by Oil Red O staining of lipid deposits. The novel nanoagent accumulated predominantly in macrophages as determined by fluorescence microscopy and flow cytometry of cells dissociated from aortas. Conclusions This report establishes the capability of a novel trimodality nanoparticle to directly detect macrophages in atherosclerotic plaques. Advantages include improved sensitivity; direct correlation of PET signal with an established biomarker (CD68); ability to readily quantify the PET signal, perform whole-body vascular surveys, and spatially localize and follow the trireporter by microscopy; and clinical translatability of the agent given similarities to magnetic resonance imaging probes in clinical trials. 10.1161/CIRCULATIONAHA.107.741181 IS - 3 JF - Circulation EP - 387 TI - Nanoparticle PET-CT Imaging of Macrophages in Inflammatory Atherosclerosis VL - 117 SP - 379 KW - 64cu-tnp KW - atherosclerosis KW - atherosclerotic-plaque KW - biodistribution KW - ccne-grant KW - dextran-coated-aminated-clio KW - flow-cytometry KW - macrophage KW - mit-mgh-ccne KW - multimodal-nanoparticle KW - pet-ct-imaging AU - Nahrendorf, Matthias AU - Zhang, Hanwen AU - Hembrador, Sheena AU - Panizzi, Peter AU - Sosnovik, David AU - Aikawa, Elena AU - Libby, Peter AU - Swirski, Filip AU - Weissleder, Ralph PY - 2008/01/22/ UR - http://dx.doi.org/10.1161/CIRCULATIONAHA.107.741181 ER -