99mTc-Labeled Nanobodies: A New Type of Targeted Probes for Imaging Antigen Expression
99mTc-Labeled Nanobodies: A New Type of Targeted Probes for Imaging Antigen Expression
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DOI：
10.2174/1874471010801010037
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发表时间：
2008-01-01
影响因子：
2.3
通讯作者：
Revets, Hilde
中科院分区：
文献类型：
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作者：
Cortez-Retamozo, Virna;Lahoutte, Tony;Revets, Hilde
针对体内分子标记物的特异性放射性标记探针的发展引起了人们的兴趣，因为靶向成像可以更准确地检测疾病。我们研究了利用（99m） Technetium标记的单链骆驼抗体（Nanobodies (R)）可变结构域对癌症抗原进行靶向成像的可行性。以抗癌胚抗原（CEA）纳米体为模型。方法：生成His(6)-CEA1纳米体，并使用Tc(I)-三羰基在His标记处用Tc-99m进行标记（Isolink, Mallinckrodt， B.V, Petten，荷兰）。通过1和3小时的离体分析评估健康胸腺小鼠的正常生物分布。在同一小鼠模型中评估cea阳性LS174T肿瘤或cea阴性A431（人皮肤癌）对照肿瘤的体内靶向性。在静脉注射90 MBq Tc-99m-His(6)-CEA1后3小时，使用配备针孔准直器的双头伽马相机进行针孔SPECT成像。结果：放射性标记效率为95%。总体生物分布表现为强烈的肾脏摄取和明显的肝脏积聚。使用针孔spect，与A431 （CEA阴性）对照肿瘤相比，LS174T （CEA阳性）中Tc-99m-His6-CEA1的平均摄取显著高于A431 （CEA阴性）对照肿瘤：分别为3.2 +/- 0.6% IA/cm(3)和1.1 +/- 0.2% IA/cm(3) （p< 0.05）。结论：本研究利用Tc(I)-羰基化学技术有效地标记了Tc-99m纳米体，显示了Tc-99m作为抗原表达成像的新型特异性探针的潜力。
Introduction: The development of specific radiolabeled probes towards molecular markers in vivo has gained interest as targeted imaging allows for a more accurate detection of diseases. We investigate the feasibility of targeted imaging of cancer antigens using the variable domain of single chain camelid antibodies (Nanobodies (R)) labeled with (99m) Technetium. Nanobodies against carcinoembryonic antigen (CEA) were used as a model.Methods: His(6)-CEA1 Nanobodies were generated and labeled with Tc-99m at their His-tag using Tc(I)-tricarbonyl (Isolink, Mallinckrodt, B.V., Petten, The Netherlands). The normal biodistribution was assessed in healthy athymic mice by ex vivo analysis at 1 and 3 h. In vivo targeting was evaluated in the same mouse model bearing the CEA-positive LS174T tumour or a CEA-negative A431 (human skin carcinoma) control tumour. Pinhole SPECT imaging was performed at 3 hours after intravenous injection of 90 MBq Tc-99m-His(6)-CEA1 using a dual-headed gamma camera equipped with pinhole collimators.Results: Radiolabeling efficiency was >95%. General biodistribution showed intense renal uptake and marked liver accumulation. Using pinhole-SPECT, the average uptake of Tc-99m-His6-CEA1 in LS174T (CEA positive) was significantly higher compared to the A431 (CEA negative) control tumour: respectively 3.2 +/- 0.6 % IA/cm(3) and 1.1 +/- 0.2 % IA/cm(3) (p< 0.05).Conclusion: This study presents effective labeling of Nanobodies with Tc-99m using Tc(I)-carbonyl chemistry and shows their potential as a new type of specific probes for imaging antigen expression.