title: Targeting P-selectin by gallium-68-labeled fucoidan positron emission tomography for noninvasive characterization of vulnerable plaques: correlation with in vivo 17.6T MRI.
abstract: OBJECTIVE
  Nuclear imaging of active plaques still remains challenging. Advanced atherosclerotic plaques have a strong expression of P-selectin by the endothelium overlying active atherosclerotic plaques, but not on the endothelium overlying inactive fibrous plaques. We proposed a new approach for noninvasive in vivo characterization of P-selectin on active plaques based on (68)Ga-Fucoidan, which is a polysaccharidic ligand of P-selectin with a nanomolar affinity.
  
  
  RESULTS
  (68)Ga-Fucoidan was tested for its potential to discriminate vulnerable plaques on apolipoprotein E-deficient mice receiving a high cholesterol diet by positron emission tomography and in correlation with 17.6T MRI. Furthermore, (68)Ga-Fucoidan was evaluated on endothelial cells in vitro and ex vivo on active plaques using autoradiography. The cellular uptake rate was increased ≈2-fold by lipopolysaccharide induction. Interestingly, on autoradiography, more intensive tracer accumulation at active plaques with thin fibrous caps and high-density foam cells were observed in comparison with a weaker focal uptake in inactive fibrous plaque segments (R=1.7±0.3; P<0.05) and fatty streaks (R=2.4±0.4; P<0.01). Strong uptake of radiotracer colocalized with increased P-selectin expression and high-density macrophage. Focal vascular uptake (mean of target to background ratio=5.1±0.8) of (68)Ga-Fucoidan was detected in all apolipoprotein E-deficient mice. Anatomic structures of plaque were confirmed by 17.6T MRI. The autoradiography showed a good agreement of (68)Ga-Fucoidan uptake with positron emission tomography.
  
  
  CONCLUSIONS
  Our data suggest that (68)Ga-Fucoidan represents a versatile imaging biomarker for P-selectin with the potential to specifically detect P-selectin expression using positron emission tomography and to discriminate vulnerable plaques in vivo.
authors.affiliation: From the Department of Nuclear Medicine (X.L., I.I., M.C.K., D.R., A.B., S.S.), Medizinische Klinik und Poliklinik I (W.B., J.W., E.B., S.F.), IFB CHFC Wuerzburg (X.L., W.B., E.B., S.F., S.S.), and Department of Experimental Physics 5 (V.H., P.J.), University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: From the Department of Nuclear Medicine (X.L., I.I., M.C.K., D.R., A.B., S.S.), Medizinische Klinik und Poliklinik I (W.B., J.W., E.B., S.F.), IFB CHFC Wuerzburg (X.L., W.B., E.B., S.F., S.S.), and Department of Experimental Physics 5 (V.H., P.J.), University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bauer
authors.affiliation: From the Department of Nuclear Medicine (X.L., I.I., M.C.K., D.R., A.B., S.S.), Medizinische Klinik und Poliklinik I (W.B., J.W., E.B., S.F.), IFB CHFC Wuerzburg (X.L., W.B., E.B., S.F., S.S.), and Department of Experimental Physics 5 (V.H., P.J.), University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Israel
authors.affiliation: From the Department of Nuclear Medicine (X.L., I.I., M.C.K., D.R., A.B., S.S.), Medizinische Klinik und Poliklinik I (W.B., J.W., E.B., S.F.), IFB CHFC Wuerzburg (X.L., W.B., E.B., S.F., S.S.), and Department of Experimental Physics 5 (V.H., P.J.), University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Kreissl
authors.affiliation: From the Department of Nuclear Medicine (X.L., I.I., M.C.K., D.R., A.B., S.S.), Medizinische Klinik und Poliklinik I (W.B., J.W., E.B., S.F.), IFB CHFC Wuerzburg (X.L., W.B., E.B., S.F., S.S.), and Department of Experimental Physics 5 (V.H., P.J.), University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Weirather
authors.affiliation: From the Department of Nuclear Medicine (X.L., I.I., M.C.K., D.R., A.B., S.S.), Medizinische Klinik und Poliklinik I (W.B., J.W., E.B., S.F.), IFB CHFC Wuerzburg (X.L., W.B., E.B., S.F., S.S.), and Department of Experimental Physics 5 (V.H., P.J.), University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Richter
authors.affiliation: From the Department of Nuclear Medicine (X.L., I.I., M.C.K., D.R., A.B., S.S.), Medizinische Klinik und Poliklinik I (W.B., J.W., E.B., S.F.), IFB CHFC Wuerzburg (X.L., W.B., E.B., S.F., S.S.), and Department of Experimental Physics 5 (V.H., P.J.), University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bauer
authors.affiliation: From the Department of Nuclear Medicine (X.L., I.I., M.C.K., D.R., A.B., S.S.), Medizinische Klinik und Poliklinik I (W.B., J.W., E.B., S.F.), IFB CHFC Wuerzburg (X.L., W.B., E.B., S.F., S.S.), and Department of Experimental Physics 5 (V.H., P.J.), University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Herold
authors.affiliation: From the Department of Nuclear Medicine (X.L., I.I., M.C.K., D.R., A.B., S.S.), Medizinische Klinik und Poliklinik I (W.B., J.W., E.B., S.F.), IFB CHFC Wuerzburg (X.L., W.B., E.B., S.F., S.S.), and Department of Experimental Physics 5 (V.H., P.J.), University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Jakob
authors.affiliation: From the Department of Nuclear Medicine (X.L., I.I., M.C.K., D.R., A.B., S.S.), Medizinische Klinik und Poliklinik I (W.B., J.W., E.B., S.F.), IFB CHFC Wuerzburg (X.L., W.B., E.B., S.F., S.S.), and Department of Experimental Physics 5 (V.H., P.J.), University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Buck
authors.affiliation: From the Department of Nuclear Medicine (X.L., I.I., M.C.K., D.R., A.B., S.S.), Medizinische Klinik und Poliklinik I (W.B., J.W., E.B., S.F.), IFB CHFC Wuerzburg (X.L., W.B., E.B., S.F., S.S.), and Department of Experimental Physics 5 (V.H., P.J.), University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Frantz
authors.affiliation: From the Department of Nuclear Medicine (X.L., I.I., M.C.K., D.R., A.B., S.S.), Medizinische Klinik und Poliklinik I (W.B., J.W., E.B., S.F.), IFB CHFC Wuerzburg (X.L., W.B., E.B., S.F., S.S.), and Department of Experimental Physics 5 (V.H., P.J.), University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Samuel
authors.initials: S
authors.lastname: Samnick
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D002791:Cholesterol, Dietary; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005710:Gallium Radioisotopes / Q000493:pharmacokinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D057054:Molecular Imaging / Q000379:methods*; D058226:Plaque, Atherosclerotic; D011134:Polysaccharides / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012422:Rupture, Spontaneous; D051149:Selenoprotein P / Q000378:metabolism*; D012720:Severity of Illness Index; D014018:Tissue Distribution
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D002791:Cholesterol, Dietary; D005710:Gallium Radioisotopes; D008070:Lipopolysaccharides; D011134:Polysaccharides; D019275:Radiopharmaceuticals; D051149:Selenoprotein P; C007789:fucoidan
keywords: Ga-68-Fucoidan; P-selectin; PET-imaging; atherosclerosis; plaque