Imaging of HER2/neu-positive BT-474 human breast cancer xenografts in athymic mice using 111In-trastuzumab (Herceptin) Fab fragments. Nucl Med Biol

Division of Nuclear Medicine, University Health Network, Toronto, Ontario, M5G 2C4, Canada.
Nuclear Medicine and Biology (Impact Factor: 2.41). 01/2005; 32(1):51-8. DOI: 10.1016/j.nucmedbio.2004.08.003
Source: PubMed


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.

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    • "HCT-116 cells over-express EGFR on their cellular surface [28]. BT-474 cells (breast ductal carcinoma) were cultured in RPMI- 1640 medium (PAA Laboratories, Pasching, Austria) supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin. BT-474 cells are reported to over-express HER2 [29]. Cells were grown in humidified incubators at 5% CO 2 and 37 C. "
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