使用（111）铟标记的曲妥珠单抗（赫赛汀）Fab片段对无胸腺小鼠体内HER2/neu阳性BT-474人乳腺癌异种移植瘤进行成像。
Imaging of HER2/neu-positive BT-474 human breast cancer xenografts in athymic mice using (111)In-trastuzumab (Herceptin) Fab fragments.
作者信息
Tang Ying, Wang Judy, Scollard Deborah A, Mondal Hridya, Holloway Claire, Kahn Harriette J, Reilly Raymond M
机构信息
Division of Nuclear Medicine, University Health Network, Toronto, Ontario, M5G 2C4, Canada.
出版信息
Nucl Med Biol. 2005 Jan;32(1):51-8. doi: 10.1016/j.nucmedbio.2004.08.003.
Trastuzumab (Herceptin) Fab were prepared by digestion of intact IgG with immobilized papain, derivatized with diethylenetriaminepentaacetic acid (DTPA) and radiolabeled with (111)In. The dissociation constant (Kd) for binding of Fab to HER2/neu-positive SK-BR-3 human breast cancer cells was two- to threefold higher than for intact IgG (14-36 vs. 8-14 nM). The binding affinity was not significantly decreased after DTPA derivatization (Kd=47 nM). (111)In-trastuzumab Fab localized specifically in HER2/neu-positive BT-474 human breast cancer xenografts in athymic mice with tumor uptake of 7.8+/-0.7% injected dose (ID)/g and tumor/blood ratio of 25.2+/-1.6 at 72 h postinjection compared with 2.7+/-0.7% ID/g and 7.0+/-0.9 for (111)In-HuM195 anti-CD33 Fab (significantly different, P<.001). Small (3-5 mm in diameter) BT-474 tumors were imaged with (111)In-trastuzumab Fab as early as 24 h postinjection.
曲妥珠单抗（赫赛汀）Fab片段是通过用固定化木瓜蛋白酶消化完整的IgG制备而成，用二乙烯三胺五乙酸（DTPA）进行衍生化，并用铟-111（¹¹¹In）进行放射性标记。Fab片段与HER2/neu阳性的SK-BR-3人乳腺癌细胞结合的解离常数（Kd）比完整的IgG高两到三倍（分别为14 - 36 nM和8 - 14 nM）。DTPA衍生化后结合亲和力没有显著降低（Kd = 47 nM）。铟-111（¹¹¹In）标记的曲妥珠单抗Fab片段特异性定位于无胸腺小鼠体内HER2/neu阳性的BT-474人乳腺癌异种移植瘤中，注射后72小时肿瘤摄取量为7.8±0.7%注射剂量（ID）/克，肿瘤/血液比值为25.2±1.6，相比之下，铟-111（¹¹¹In）标记的抗CD33 Fab片段HuM195的肿瘤摄取量为2.7±0.7% ID/克，肿瘤/血液比值为7.0±0.9（差异显著，P<0.001）。直径3 - 5毫米的小BT-474肿瘤在注射铟-111（¹¹¹In）标记的曲妥珠单抗Fab片段后最早24小时就能成像。
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