Detection of inflamed atherosclerotic lesions with diadenosine-5′,5′′′-P1,P4-tetraphosphate (AP4A) and positron-emission tomography

被引:24
作者
Elmaleh, D. R.
Fischman, A. J.
Tawakol, A.
Zhu, A.
Shoup, T. M.
Hoffmann, U.
Brownell, A. -L
Zamecnik, P. C.
机构
[1] Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA
[2] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA
[3] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02114 USA
关键词
atherosclerosis; vascular damage; plaque imaging;
D O I
10.1073/pnas.0607246103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Diadenosine-5', 5"'-P-1, P-4-tetraphosphate (Ap(4)A) and its analog P-2,P-3-monochloromethylene diadenosine-5',5"'-P-1,P-4-tetraphosphate (AppCHClppA) are competitive inhibitors of adenosine diphosphate-induced platelet aggregation, which plays a central role in arterial thrombosis and plaque formation. In this study, we evaluate the imaging capabilities of positron-emission tomography (PET) with P-2,P-3-[F-18]monofluoromethylene diadenosine-5',5'"-P-1,P-4-tetraphosphate ([F-18]AppCHFppA) to detect atherosclerotic lesions in male New Zealand White rabbits. Three to six months after balloon injury to the aorta, the rabbits were injected with [F-18]AppCHFppA, and microPET imaging showed rapid accumulation of this radiopharmaceutical in the atherosclerotic abdominal aorta, with lesions clearly visible 30 min after injection. Computed tomographic images were coregistered with PET images to improve delineation of aortoiliac tracer activity. Plaque macrophage density, quantified by immunostaining with RAM11 against rabbit macrophages, correlated with PET measurements of [F-18]AppCHFppA uptake (r = 0.87, P < 0.0001), whereas smooth-muscle cell density, quantified by immunostaining with 1A4 against smooth muscle actin, did not. Biodistribution studies of [F-18]AppCHFppA in normal rats indicated typical adenosine dinucleotide behavior with insignificant myocardial uptake and fast kidney clearance. The accumulation of [F-18]AppCHFppA in macrophage-rich atherosclerotic plaques can be quantified noninvasively with PET. Hence, [F-18]AppCHFppA holds promise for the noninvasive characterization of vascular inflammation.
引用
收藏
页码:15992 / 15996
页数:5
相关论文
共 34 条
[1]   Insights into the use of paramagnetic Gd(III) complexes in MR-molecular imaging investigations [J].
Aime, S ;
Cabella, C ;
Colombatto, S ;
Crich, SG ;
Gianolio, E ;
Maggioni, F .
JOURNAL OF MAGNETIC RESONANCE IMAGING, 2002, 16 (04) :394-406
[2]  
BAUMGARTNER H. R., 1963, ZEIT GES EXPTL MED, V137, P227, DOI 10.1007/BF02045498
[3]  
Blackburn GM, 1992, AP4A OTHER DINUCLEOS, P305
[4]   Overview of the P2 receptors [J].
Boeynaems, JM ;
Communi, D ;
Gonzalez , NS ;
Robaye, B .
SEMINARS IN THROMBOSIS AND HEMOSTASIS, 2005, 31 (02) :139-149
[5]   LEUKOCYTE-ENDOTHELIAL CELL RECOGNITION - 3 (OR MORE) STEPS TO SPECIFICITY AND DIVERSITY [J].
BUTCHER, EC .
CELL, 1991, 67 (06) :1033-1036
[6]   Coronary artery disease: Improved reproducibility of calcium scoring with an electron-beam CT volumetric method [J].
Callister, TQ ;
Cooil, B ;
Raya, SP ;
Lippolis, NJ ;
Russo, DJ ;
Raggi, P .
RADIOLOGY, 1998, 208 (03) :807-814
[7]   The pyrimidinergic P2Y6 receptor mediates a novel release of proinflammatory cytokines and chemokines in monocytic cells stimulated with UDP [J].
Cox, MA ;
Gomes, B ;
Palmer, K ;
Du, K ;
Wiekowski, M ;
Wilburn, B ;
Petro, M ;
Chou, CC ;
Desquitado, C ;
Schwarz, M ;
Lunn, C ;
Lundell, D ;
Narula, SK ;
Zavodny, PJ ;
Jenh, CH .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 330 (02) :467-473
[8]   SCINTIGRAPHIC DETECTION OF CAROTID ATHEROSCLEROSIS WITH INDIUM-111-LABELED AUTOLOGOUS PLATELETS [J].
DAVIS, HH ;
SIEGEL, BA ;
SHERMAN, LA ;
HEATON, WA ;
NAIDICH, TP ;
JOIST, JH ;
WELCH, MJ .
CIRCULATION, 1980, 61 (05) :982-988
[9]   Rapid noninvasive detection of experimental atherosclerotic lesions with novel 99mTc-labeled diadenosine tetraphosphates [J].
Elmaleh, DR ;
Narula, J ;
Babich, JW ;
Petrov, A ;
Fischman, AJ ;
Khaw, BA ;
Rapaport, E ;
Zamecnik, PC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (02) :691-695
[10]   TC-99M-LABELED NUCLEOTIDES AS TUMOR-SEEKING RADIODIAGNOSTIC AGENTS [J].
ELMALEH, DR ;
ZAMECNIK, PC ;
CASTRONOVO, FP ;
STRAUSS, HW ;
RAPAPORT, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (03) :918-921