用于黑色素瘤靶向放疗的166Ho和90Y标记的6D2单克隆抗体：与188Re放射性标记的比较
166Ho and 90Y labeled 6D2 monoclonal antibody for targeted radiotherapy of melanoma: comparison with 188Re radiolabel.
作者信息
Thompson S, Ballard B, Jiang Z, Revskaya E, Sisay N, Miller W H, Cutler C S, Dadachova E, Francesconi L C
机构信息
Department of Chemistry, Hunter College of the City University of New York, 695 Park Avenue, New York, NY 10065, USA.
Department of Chemistry, Hunter College of the City University of New York, 695 Park Avenue, New York, NY 10065, USA.
出版信息
Nucl Med Biol. 2014 Mar;41(3):276-81. doi: 10.1016/j.nucmedbio.2013.12.015. Epub 2013 Dec 30.
INTRODUCTION
An approach to radioimmunotherapy (RIT) of metastatic melanoma is the targeting of melanin pigment with monoclonal antibodies (mAbs) to melanin radiolabeled with therapeutic radionuclides. The proof of principle experiments were performed using a melanin-binding antibody 6D2 of IgM isotype radiolabeled with a β emitter (188)Re and demonstrated the inhibition of tumor growth. In this study we investigated the efficacy of 6D2 antibody radiolabeled with two other longer lived β emitters (90)Y and (166)Ho in treatment of experimental melanoma, with the objective to find a possible correlation between the efficacy and half-life of the radioisotopes which possess high energy β (E(max)>1.5 MeV) emission properties.
METHODS
6D2 was radiolabeled with longer lived β emitters (90)Y and (166)Ho in treatment of experimental melanoma in A2058 melanoma tumor-bearing nude mice. The immunoreactivity of the radiolabeled 6D2 mAb, its in vitro binding to the MNT1 human melanoma cells, the biodistribution and therapy in A2058 human melanoma bearing nude mice as well as dosimetry calculations were performed.
RESULTS
When labeled with the longer lived (90)Y radionuclide, the 6D2 mAb did not produce any therapeutic effect in tumor bearing mice while the reduction of the tumor growth by (166)Ho-6D2 was very similar to the previously reported therapy results for (188)Re-6D2. In addition, (166)Ho-labeled mAb produced the therapeutic effect on the tumor without any toxic effects while the administration of the (90)Y-labeled radioconjugate was toxic to mice with no appreciable anti-tumor effect.
CONCLUSIONS
(166)Ho-labeled mAb to melanin produced some therapeutic effect on the tumor without any toxic effects while the administration of the (90)Y-labeled radioconjugate was toxic to mice with no appreciable anti-tumor effect. We concluded that the serum half-life of the 6D2 carrier antibody matched well the physical half-life of (166)Ho to deliver the tumoricidal absorbed dose to the tumor. Further investigation of this radionuclide for RIT of melanoma is warranted.
引言
转移性黑色素瘤的放射免疫疗法（RIT）的一种方法是用与治疗性放射性核素进行放射性标记的针对黑色素的单克隆抗体（mAb）来靶向黑色素。原理验证实验使用了用β发射体（188）Re进行放射性标记的IgM同种型黑色素结合抗体6D2，并证明了对肿瘤生长的抑制作用。在本研究中，我们研究了用另外两种半衰期更长的β发射体（90）Y和（166）Ho进行放射性标记的6D2抗体在实验性黑色素瘤治疗中的疗效，目的是找出具有高能β（E（max）>1.5 MeV）发射特性的放射性同位素的疗效与半衰期之间可能存在的相关性。
方法
用半衰期更长的β发射体（90）Y和（166）Ho对6D2进行放射性标记，用于治疗荷A2058黑色素瘤肿瘤的裸鼠的实验性黑色素瘤。进行了放射性标记的6D2 mAb的免疫反应性、其与MNT1人黑色素瘤细胞的体外结合、在荷A2058人黑色素瘤裸鼠中的生物分布和治疗以及剂量学计算。
结果
当用半衰期更长的（90）Y放射性核素进行标记时，6D2 mAb在荷瘤小鼠中未产生任何治疗效果，而（166）Ho-6D2对肿瘤生长的抑制作用与先前报道的（188）Re-6D2的治疗结果非常相似。此外，（166）Ho标记的mAb对肿瘤产生了治疗效果且无任何毒性作用，而给予（90）Y标记的放射性偶联物对小鼠有毒性且无明显的抗肿瘤作用。
结论
（166）Ho标记的黑色素mAb对肿瘤产生了一定的治疗效果且无任何毒性作用，而给予（90）Y标记的放射性偶联物对小鼠有毒性且无明显的抗肿瘤作用。我们得出结论，6D2载体抗体的血清半衰期与（166）Ho的物理半衰期匹配良好，从而能够向肿瘤递送杀肿瘤吸收剂量。有必要对这种放射性核素用于黑色素瘤的放射免疫疗法进行进一步研究。
Zotero 插件