Amplified delivery of indium-111 to EGFR-positive human breast cancer cells.
A method is described to amplify the delivery of 111In to human breast cancer cells utilizing a novel human serum albumin-human EGF (HSA-hEGF) bioconjugate substituted preferentially in the HSA domain with multiple DTPA metal chelators for 111In. 111In-DTPA-HSA-hEGF exhibited a lower receptor-binding affinity than 111In-DTPA-hEGF but was rapidly and specifically bound, internalized and translocated to the nucleus in EGFR-positive MDA-MB-468 breast cancer cells. 111In-DTPA-HSA-hEGF was cytotoxic in vitro mainly through the emission of short-range Auger electrons and partially through the effects of the hEGF moiety to MDA-MB-468 cells overexpressing EGFR (1-2 x 10(6) receptors/cell) but not towards MCF-7 breast cancer cells with a 100-fold lower level of EGFR on their surface. The cytotoxicity in vitro against MDA-MB-468 cells of 111In-DTPA-HSA-hEGF substituted with nine DTPA chelators was enhanced 4-fold compared to 111In-DTPA-hEGF monosubstituted with DTPA. Studies are planned to further evaluate 111In-DTPA-HSA-hEGF in vivo as a new imaging and targeted radiotherapeutic agent for breast cancer.
Wang
J
J
Division of Nuclear Medicine, University Health Network, Toronto General Hospital, Toronto, ON, Canada.
Chen
P
P
Su
Z F
ZF
Vallis
K
K
Sandhu
J
J
Cameron
R
R
Hendler
A
A
Reilly
R M
RM
D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D007205:Indium Radioisotopes / Q000008:administration & dosage / Q000627:therapeutic use*; D011869:Radioligand Assay; D011877:Radionuclide Imaging; D012709:Serum Albumin / Q000378:metabolism*
D007205:Indium Radioisotopes; D012709:Serum Albumin; D066246:ErbB Receptors