Signal amplification in molecular imaging by pretargeting a multivalent, bispecific antibody.
Here we describe molecular imaging of cancer using signal amplification of a radiotracer in situ by pretargeting a multivalent, bispecific antibody to carcinoembryonic antigen (CEA), which subsequently also captures a radioactive hapten-peptide. Human colon cancer xenografts as small as approximately 0.15 g were disclosed in nude mice within 1 h of giving the radiotracer, with tumor/blood ratios increased by >or=40-fold (approximately 10:1 at 1 h, approximately 100:1 at 24 h), compared to a (99m)Tc-labeled CEA-specific F(ab') used clinically for colorectal cancer detection, while also increasing tumor uptake tenfold ( approximately 20% injected dose/g) under optimal conditions. This technology could be adapted to other antibodies and imaging modalities.
Sharkey
Robert M
RM
Garden State Cancer Center, Center for Molecular Medicine and Immunology, 520 Belleville Avenue, Belleville, New Jersey 07109, USA.
Cardillo
Thomas M
TM
Rossi
Edmund A
EA
Chang
Chien-Hsing
CH
Karacay
Habibe
H
McBride
William J
WJ
Hansen
Hans J
HJ
Horak
Ivan D
ID
Goldenberg
David M
DM
D000818:Animals; D018033:Antibodies, Bispecific / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000276:immunology / Q000378:metabolism; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy; D011877:Radionuclide Imaging; D013667:Technetium / Q000493:pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D018033:Antibodies, Bispecific; D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes; D013667:Technetium