Fontan Charlotte, Bezombes Christine, Salabert Anne Sophie, Costes Julien, Lopez Raphael, Fournie Jean-Jacques, Avet-Loiseau Hervé, Coulais Yvon, Payoux Pierre, Tafani Mathieu
Radiopharmacy, University Hospital, Toulouse, France.
The Cancer Research Center of Toulouse, Toulouse, France.
J Labelled Comp Radiopharm. 2015 Jun 15;58(7):274-80. doi: 10.1002/jlcr.3283. Epub 2015 May 27.
Lymphomas are the most frequent haematological malignancy. In non-Hodgkin's lymphomas (NHL), more than 90% of tumor cells express the cluster of differentiation (CD) 20 antigen. At the end of frontline therapy, the evaluation of remission is based on computed tomography (CT) and positron emission tomography coupled with computer tomography (PET/CT) with [(18)F]-fluorodeoxyglucose ([(18)F]FDG). Unfortunately, these techniques are not specific and cannot distinguish residual active tumor from inflammation. The aim of this study was to develop a specific radiotracer of NHL CD 20+ cells for clinical applications. The radiolabelling technique presented, based on the use of tricarbonyl compound, does not include an antibody reduction because this step could damage the protein. Actually, rituximab, an anti-CD 20 chimeric antibody used for the treatment of these NHL, was radiolabelled with Isolink® (99m)Tc-tricarbonyl compound in a three-step procedure without using a specific antibody reducer. Radiolabelling yield was greater than 97%. In vitro experiments showed a conservation of antibody integrity. In vivo experiments using Single-photon emission computed tomography/CT showed significant tumor targeting 24 h after injection of the radiotracer. It was consequently possible to develop an immunoradiolabelling method to specifically detect the residual disease. As this procedure is fast, reproducible and gentle, it will be possible to comply with Good Manufacturing Practices.
淋巴瘤是最常见的血液系统恶性肿瘤。在非霍奇金淋巴瘤（NHL）中，超过90%的肿瘤细胞表达分化簇（CD）20抗原。一线治疗结束时，缓解评估基于计算机断层扫描（CT）以及正电子发射断层扫描与计算机断层扫描联用（PET/CT），使用[（18）F] - 氟脱氧葡萄糖（[（18）F]FDG）。不幸的是，这些技术并不特异，无法区分残留的活性肿瘤与炎症。本研究的目的是开发一种用于临床应用的NHL CD 20 +细胞特异性放射性示踪剂。所呈现的放射性标记技术基于三羰基化合物的使用，不包括抗体还原步骤，因为这一步骤可能会损害蛋白质。实际上，利妥昔单抗是一种用于治疗这些NHL的抗CD 20嵌合抗体，通过三步程序用Isolink®（99m）Tc - 三羰基化合物进行放射性标记，无需使用特异性抗体还原剂。放射性标记产率大于97%。体外实验表明抗体完整性得以保留。使用单光子发射计算机断层扫描/CT的体内实验显示，注射放射性示踪剂后24小时肿瘤有显著靶向性。因此，有可能开发一种免疫放射性标记方法来特异性检测残留疾病。由于该程序快速、可重复且温和，将有可能符合药品生产质量管理规范。
