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

Trastuzumab (Herceptin) Fab were prepared by digestion of intact IgG with immobilized papain, derivatized with diethylenetriamine-pentaacetic acid (DTPA) and radiolabeled with In-111. The dissociation constant (K-d) 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 (K-d = 47 nM). In-111-trastuzumab Fab localized specifically in HER2/neu-positive BT-474 human breast cancer xenoarafts 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 In-111-HuM195 anti-CD33 Fab (significantly different, P < .001). Small (3-5 mm in diameter) BT-474 tumors were imaged with In-111-trastuzumab Fab as early as 24 h postinjection. (C) 2005 Elsevier Inc. All rights reserved.