Lederman R J, Raylman R R, Fisher S J, Kison P V, San H, Nabel E G, Wahl R L
Department of Medicine, University of Michigan Health System, Ann Arbor, USA.
Nucl Med Commun. 2001 Jul;22(7):747-53. doi: 10.1097/00006231-200107000-00004.
Inflammation contributes to atherosclerotic plaque remodeling, enlargement and rupture. Non-invasive imaging of coronary artery inflammation could help target therapy to 'vulnerable' atheromata, but is limited because of small tissue mass and arterial motion. Local radiopharmaceutical imaging may overcome some of these limitations. We used a positron-sensitive fiberoptic probe, which can distinguish positron emissions from annihilation photons, to identify diseased from healthy endothelium in an atherosclerotic model. New Zealand White rabbits underwent Fogarty-catheter injury of an iliac artery and then were fed a high-fat diet for 3 weeks. Fasted animals received 90-180 MBq of 18-fluorodeoxyglucose (FDG) 2-4 h before sacrifice and harvest of injured and uninjured iliacs. Arteries were incised longitudinally and the probe was placed in contact with the arterial intima. Multiple measurements were obtained along 1 cm artery segments in 60 s intervals, and corrected for 18F decay and background. Measurements were recorded over 93 injured and normal artery segments in 11 animals. Mean probe Z-scores were 4.8-fold higher (CI 3.4-6.3) over injury atherosclerosis compared with uninjured normal iliac artery segments (P<0.001). Gamma counting confirmed that injured artery segments accumulated more FDG per gram than did normal segments (0.203% x kg injected dose per gram of tissue versus 0.042, P<0.001). Non-arterial tissue also accumulated FDG avidly, particularly reticuloendothelial tissues and blood. Delayed sacrifice, 4 h compared with 2 h after animal FDG injection, further reduced blood background counts and improved the signal-to-noise ratio. Histopathology confirmed that injured iliac artery had significantly higher intimal and medial cross-sectional area compared with uninjured artery. Injured artery also had significantly higher macrophage and smooth muscle cell density. Positron-sensitive probe counts correlated with the intima to media ratio (r =0.63, P = 0.03). Our positron-sensitive probe distinguishes atherosclerotic from healthy artery in a blood-free field. Intravascular study of plaque biology may be feasible using FDG and a positron-sensitive probe.
炎症促进动脉粥样硬化斑块的重塑、增大和破裂。冠状动脉炎症的非侵入性成像有助于将治疗靶向于“易损”粥样斑块，但由于组织量小和动脉运动而受到限制。局部放射性药物成像可能会克服其中一些限制。我们使用了一种正电子敏感光纤探头，它可以区分正电子发射与湮灭光子，以在动脉粥样硬化模型中识别病变内皮与健康内皮。新西兰白兔接受了髂动脉的Fogarty导管损伤，然后喂食高脂饮食3周。禁食动物在处死并收获受伤和未受伤的髂动脉前2 - 4小时接受90 - 180 MBq的18 - 氟脱氧葡萄糖（FDG）。动脉纵向切开，探头与动脉内膜接触。在60秒间隔内沿着1厘米动脉段进行多次测量，并对18F衰变和本底进行校正。在11只动物中对93个受伤和正常动脉段进行了测量。与未受伤的正常髂动脉段相比，损伤动脉粥样硬化的平均探头Z分数高4.8倍（CI 3.4 - 6.3）（P<0.001）。γ计数证实，受伤动脉段每克积累的FDG比正常段更多（每克组织0.203%×千克注射剂量对0.042，P<0.001）。非动脉组织也大量积累FDG，特别是网状内皮组织和血液。与动物注射FDG后2小时相比，延迟4小时处死进一步降低了血液本底计数并提高了信噪比。组织病理学证实，受伤的髂动脉与未受伤的动脉相比，内膜和中膜横截面积显著更高。受伤动脉的巨噬细胞和平滑肌细胞密度也显著更高。正电子敏感探头计数与内膜中膜比相关（r = 0.63，P = 0.03）。我们的正电子敏感探头在无血区域可区分动脉粥样硬化与健康动脉。使用FDG和正电子敏感探头进行斑块生物学的血管内研究可能是可行的。
