Carrió I, Pieri P L, Narula J, Prat L, Riva P, Pedrini L, Pretolani E, Caruso G, Sarti G, Estorch M, Berná L, Riambau V, Matías-Guiu X, Pak C, Ditlow C, Chen F, Khaw B A
Department of Nuclear Medicine, Hospital de Sant Pau, Barcelona, Spain.
J Nucl Cardiol. 1998 Nov-Dec;5(6):551-7. doi: 10.1016/s1071-3581(98)90108-8.
Targeting exclusive antigens in atherosclerotic plaques with antibodies may provide a noninvasive means to detect rapidly proliferative atherosclerotic lesions. 111In-labeled negative charge-modified Z2D3 F(ab')2 (Z2D3) specific for an antigen expressed exclusively by proliferating smooth muscle cells has been shown to accumulate in rabbit atherosclerotic plaques.
The safety, biodistribution, accumulation, and elimination of Z2D3 were assessed in 11 patients who were candidates for carotid endarterectomy. The presence of atheromas in these patients was confirmed by angiography and Doppler ultrasound. Z2D3 (250 microg) labeled with 5 mCi of 111In was administered by slow intravenous injection. Planar and single photon emission computed tomography (SPECT) images were obtained 4, 24, 48, and 72 hours later. Carotid endarterectomy was performed and the surgical specimens were imaged, weighed, gamma-counted, and analyzed by immunostaining.
Uptake of Z2D3 at the site of the carotid plaques was observed in the planar and SPECT views at 4 hours in all subjects. In addition, antibody uptake was noted in the contralateral vessel in 5 subjects. SPECT images identified the atherosclerotic plaques with focal uptake. The antibody uptake corresponded with the angiographic location of the disease. Immunohistochemical studies of the endarterectomy specimens confirmed the localization of Z2D3 into the plaque areas containing smooth muscle cells. Adverse drug reactions were not observed.
This study demonstrates the feasibility of targeting atherosclerotic lesions with negative charge-modified antibody. It also proposes the possibility of selective identification of various components of atherosclerotic plaque, which may contribute to determining strategies of intervention in future.
用抗体靶向动脉粥样硬化斑块中的特异性抗原可能提供一种检测快速增殖性动脉粥样硬化病变的非侵入性方法。已证实，针对仅由增殖性平滑肌细胞表达的抗原的111In标记的负电荷修饰Z2D3 F(ab')2（Z2D3）可在兔动脉粥样硬化斑块中积聚。
在11例适合行颈动脉内膜切除术的患者中评估Z2D3的安全性、生物分布、积聚和清除情况。通过血管造影和多普勒超声确认这些患者存在动脉粥样硬化斑块。缓慢静脉注射用5 mCi的111In标记的Z2D3（250微克）。在4、24、48和72小时后获取平面和单光子发射计算机断层扫描（SPECT）图像。进行颈动脉内膜切除术，对手术标本进行成像、称重、γ计数，并通过免疫染色进行分析。
在所有受试者中，4小时时在平面和SPECT图像上均观察到Z2D3在颈动脉斑块部位的摄取。此外，5名受试者的对侧血管中也发现有抗体摄取。SPECT图像通过局灶性摄取识别出动脉粥样硬化斑块。抗体摄取与疾病的血管造影位置相符。对内膜切除术标本的免疫组织化学研究证实Z2D3定位于含有平滑肌细胞的斑块区域。未观察到药物不良反应。
本研究证明了用负电荷修饰抗体靶向动脉粥样硬化病变的可行性。它还提出了选择性识别动脉粥样硬化斑块各种成分的可能性，这可能有助于确定未来的干预策略。
