Imaging of HER2/neu-positive BT-474 human breast cancer xenografts in athymic mice using (111)In-trastuzumab (Herceptin) Fab fragments.
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.
Tang
Ying
Y
Division of Nuclear Medicine, University Health Network, Toronto, Ontario, M5G 2C4, Canada.
Wang
Judy
J
Scollard
Deborah A
DA
Mondal
Hridya
H
Holloway
Claire
C
Kahn
Harriette J
HJ
Reilly
Raymond M
RM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D014018:Tissue Distribution; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D007140:Immunoglobulin Fab Fragments; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab