A comparison of 67Cu- and 131I-labelled forms of monoclonal antibodies SEN7 and SWA20 directed against small-cell lung cancer.
The intact anti-SCLC monoclonal antibody (MAb) SEN7 and its F(ab')2 were labelled with the beta-emitting isotope 67Cu. Both materials retained their biological activity in vitro as determined by the Lindmo assay. In a direct comparison of in vivo distribution in a xenograph model, 131I- and 67Cu-labelled intact SEN7 showed similar absolute tumour accumulation. Blood levels were markedly lower in the case of the 67Cu-labelled antibody, resulting in improved tumour:blood ratios which reached a maximum of 13:1 compared with only 4.5:1 for 131I-SEN7. In the case of the 67Cu-labelled F(ab')2, very high accumulation of the nuclide was observed in the kidney. Levels of radio copper in liver and spleen were also found to be significantly raised when compared with radio iodine. SWA20, a MAb which had previously failed to show any selective in vivo accumulation in tumour xenografts when labelled with radio iodine showed higher and more stable tumour accumulation when labelled with 67Cu.
Smith
A
A
Division of Radiopharmacy, Paul Scherrer Institute, Würenlingen, Switzerland.
Zangemeister-Wittke
U
U
Waibel
R
R
Schenker
T
T
Schubiger
P A
PA
Stahel
R A
RA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000000981:diagnostic imaging*; D003301:Copper Radioisotopes / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000378:metabolism; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging*; D051379:Mice / Q000276:immunology; D008819:Mice, Nude; D016719:Radioimmunodetection / Q000379:methods*; D013997:Time Factors; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D003301:Copper Radioisotopes; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes