Paganelli G, Magnani P, Zito F, Lucignani G, Sudati F, Truci G, Motti E, Terreni M, Pollo B, Giovanelli M
INB-CNR, University of Milan, Department of Nuclear Medicine, Scientific Institute H San Raffaele, Italy.
Eur J Nucl Med. 1994 Apr;21(4):314-21. doi: 10.1007/BF00947966.
The imaging of cerebral gliomas with radiolabelled monoclonal antibodies (MoAbs) has been previously reported. However, previous studies have been hampered by the drawback of a low tumour to non-tumour ratio. In order to overcome this problem we have developed a three-step pre-targeting method using the avidin-biotin system. The rationale of this technique consists in vivo labelling of biotinylated MoAbs targeted onto tumour deposits, when most of the unbound antibodies have been cleared from the bloodstream as avidin-bound complexes. The anti-tenascin MoAb BC2, specific for the majority of gliomas, was biotinylated and 1 mg was administered i.v. in 20 patients with histologically documented cerebral lesions. After 24-36 h, 5 mg avidin was injected i.v. followed 24 h later by a third i.v. injection of 0.2 mg PnAO-biotin labelled with 15-20 mCi technetium-99m. No evidence of toxicity was observed. Whole-body biodistribution was measured at 20 min, 3 h and 5 h post-injection. [99mTc]PnAO-biotin had a fast blood clearance and was primarily excreted through the biliary system. A dedicated single-photon emission tomography system was used to acquire brain tomographic images 1-2 h after the administration of [99mTc]PnAO-biotin. Tumours were detected in 15/18 glioma patients with a tumour to non-tumour ratio of up 14:1. This three-step method, based on the sequential administration of anti-tenascin MoAb BC2, avidin and [99mTc]PnAO-biotin, can support computed tomography or magnetic resonance imaging for the diagnosis and follow-up of patients with glioma. Further studies are required to evaluate the potential of this technique for therapeutic application.
先前已有关于用放射性标记单克隆抗体（MoAbs）对脑胶质瘤进行成像的报道。然而，先前的研究因肿瘤与非肿瘤比例低这一缺点而受到阻碍。为了克服这个问题，我们开发了一种使用抗生物素蛋白-生物素系统的三步预靶向方法。该技术的原理是，当大多数未结合的抗体以抗生物素蛋白结合复合物的形式从血液中清除后，在体内对靶向肿瘤沉积物的生物素化MoAbs进行标记。对大多数胶质瘤具有特异性的抗腱生蛋白MoAb BC2被生物素化，1毫克通过静脉注射给予20例经组织学证实有脑病变的患者。24 - 36小时后，静脉注射5毫克抗生物素蛋白，24小时后再静脉注射第三次，注射0.2毫克用15 - 20毫居里锝- 99m标记的PnAO - 生物素。未观察到毒性迹象。在注射后20分钟、3小时和5小时测量全身生物分布。[99mTc]PnAO - 生物素具有快速的血液清除率，主要通过胆道系统排泄。在给予[99mTc]PnAO - 生物素后1 - 2小时，使用专用的单光子发射断层扫描系统获取脑部断层图像。在18例胶质瘤患者中的15例检测到肿瘤，肿瘤与非肿瘤比例高达14:1。这种基于依次给予抗腱生蛋白MoAb BC2、抗生物素蛋白和[99mTc]PnAO - 生物素的三步方法，可辅助计算机断层扫描或磁共振成像用于胶质瘤患者的诊断和随访。需要进一步研究来评估该技术在治疗应用方面的潜力。
