Lanza G M, Wallace K D, Scott M J, Cacheris W P, Abendschein D R, Christy D H, Sharkey A M, Miller J G, Gaffney P J, Wickline S A
Department of Medicine, Barnes-Jewish Hospital of St Louis, MO 63130, USA.
Circulation. 1996 Dec 15;94(12):3334-40. doi: 10.1161/01.cir.94.12.3334.
In this work, we report a novel targetable ultrasonic contrast agent with the potential to noninvasively define and localize myriad pathological tissues for diagnosis or therapy. The agent is a biotinylated, lipid-coated, perfluorocarbon emulsion that has low inherent echogenicity unless bound to a surface or itself.
In study 1, emulsions with and without biotin were suspended in buffered saline and imaged with a 7.5-MHz linear-array transducer. Neither emulsion manifested significant ultrasonic backscatter until avidin was added. Avidin-induced aggregation produced a marked enhancement in backscatter from the biotinylated but not from the control emulsion. In study 2, porcine fibrin clots in vitro were pretargeted with biotinylated antifibrin monoclonal antibodies and then exposed to avidin and then to biotinylated or control perfluorocarbon emulsions. The basal acoustic reflectivity of clots imaged with a 7.5-MHz linear-array transducer was uniformly low and was increased substantially by exposure to the targeted biotinylated emulsion. In study 3, partially occlusive arterial thrombi were created in dogs and then exposed to antifibrin antibodies and avidin in situ. Biotinylated or control emulsion was administered either in situ or systemically. At baseline, all thrombi were undetectable with a 7.5-MHz linear-array transducer. Thrombi exposed to antifibrin-targeted contrast exhibited increased echogenicity (P < .05); control thrombi remained acoustically undetectable.
These data provide the first in vivo demonstration of a site-specific ultrasonic contrast agent and have potential for improved sensitivity and specificity for noninvasive diagnosis of thrombi and other pathological diseases.
在本研究中，我们报告了一种新型的可靶向超声造影剂，它有潜力非侵入性地界定和定位多种病理组织以用于诊断或治疗。该造影剂是一种生物素化的、脂质包裹的全氟碳乳剂，其本身固有回声性低，除非与表面结合或自身结合。
在研究1中，将含生物素和不含生物素的乳剂悬浮于缓冲盐溶液中，并用7.5兆赫线性阵列换能器成像。在添加抗生物素蛋白之前，两种乳剂均未表现出明显的超声反向散射。抗生物素蛋白诱导的聚集使生物素化乳剂的反向散射显著增强，而对照乳剂则未增强。在研究2中，体外猪纤维蛋白凝块先用生物素化抗纤维蛋白单克隆抗体进行预靶向，然后暴露于抗生物素蛋白，再暴露于生物素化或对照全氟碳乳剂。用7.5兆赫线性阵列换能器成像的凝块的基础声反射率均较低，而暴露于靶向生物素化乳剂后显著增加。在研究3中，在犬体内制造部分闭塞性动脉血栓，然后原位暴露于抗纤维蛋白抗体和抗生物素蛋白。生物素化或对照乳剂原位或全身给药。在基线时，用7.5兆赫线性阵列换能器均无法检测到所有血栓。暴露于抗纤维蛋白靶向造影剂的血栓回声增强（P <.05）；对照血栓在声学上仍无法检测到。
这些数据首次在体内证明了一种位点特异性超声造影剂，对提高血栓和其他病理疾病的非侵入性诊断的敏感性和特异性具有潜力。
