Bailly Clément, Gouard Sébastien, Lacombe Marie, Remaud-Le Saëc Patricia, Chalopin Benjamin, Bourgeois Mickaël, Chouin Nicolas, Tripier Raphaël, Halime Zakaria, Haddad Ferid, Faivre-Chauvet Alain, Kraeber-Bodéré Françoise, Chérel Michel, Bodet-Milin Caroline
Nuclear Medicine Department, University Hospital, Nantes, France.
Nantes-Angers Cancer Research Center CRCINA, University of Nantes, INSERM UMR1232, CNRS-ERL6001, Nantes, France.
Oncotarget. 2018 Jan 3;9(10):9061-9072. doi: 10.18632/oncotarget.23886. eCollection 2018 Feb 6.
Although recent data from the literature suggest that PET imaging with [18]-Fluorodeoxyglucose (F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker in many laboratories for the identification and purification of myeloma cells, and could be used in phenotype tumor imaging. In this study, we evaluated a Cu-labeled anti-CD138 murine antibody (Cu-TE2A-9E7.4) and a metabolic tracer (CuCl) for PET imaging in a MM syngeneic mouse model.
Cu-TE2A-9E7.4 antibody and CuCl2 were evaluated via PET imaging and biodistribution studies in C57BL / KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions. These results were compared to 18F-FDG-PET imaging. Autoradiography and histology of representative tumors were secondly conducted. In biodistribution and PET studies, Cu-TE2A-9E7.4 displayed good tumor uptake of subcutaneous and intra-medullary lesions, greater than that demonstrated with F-FDG-PET. In control experiments, only low-level, non-specific uptake of Cu-labeled isotype IgG was observed in tumors. Similarly, low activity concentrations of CuCl were accumulated in MM lesions. Histopathologic analysis of the immuno-PET-positive lesions revealed the presence of plasma cell infiltrates within the bone marrow.
Cu-labeled anti-CD138 antibody can detect subcutaneous MM tumors and bone marrow lesions with high sensitivity, outperforming F-FDG-PET and CuCl in this preclinical model. These data support Cu-anti-CD138 antibody as a specific and promising new imaging radiopharmaceutical agent in MM.
尽管近期文献数据表明,[18]-氟脱氧葡萄糖(F-FDG)PET成像在多发性骨髓瘤(MM)中是一种有前景的技术,但开发其他放射性药物似乎也很有意义。CD138目前在许多实验室用作鉴定和纯化骨髓瘤细胞的标准标志物,可用于肿瘤表型成像。在本研究中,我们评估了一种铜标记的抗CD138鼠抗体(Cu-TE2A-9E7.4)和一种代谢示踪剂(CuCl)在MM同基因小鼠模型中的PET成像。
通过PET成像和生物分布研究,在携带5T33-MM皮下肿瘤或骨病变的C57BL / KaLwRij小鼠中评估了Cu-TE2A-9E7.4抗体和CuCl2。将这些结果与18F-FDG-PET成像进行比较。其次进行了代表性肿瘤的放射自显影和组织学检查。在生物分布和PET研究中,Cu-TE2A-9E7.4在皮下和髓内病变中显示出良好的肿瘤摄取,高于F-FDG-PET所显示的摄取。在对照实验中,仅在肿瘤中观察到低水平、非特异性的铜标记同型IgG摄取。同样,MM病变中积累了低活性浓度的CuCl。免疫PET阳性病变的组织病理学分析显示骨髓内存在浆细胞浸润。
在这个临床前模型中,铜标记的抗CD138抗体能够高灵敏度地检测皮下MM肿瘤和骨髓病变,优于F-FDG-PET和CuCl。这些数据支持Cu-抗CD138抗体作为MM中一种特异性且有前景的新型成像放射性药物。