Preadsorption of radiolabeled monoclonal antibodies to liver and spleen tissues leads to higher tumor-to-normal-tissue ratios.
This study addresses the impact of background activity on the use of radioimmunoconjugates for radioimmunodiagnosis and radioimmunotherapy. Since the liver and the spleen represent organs with preferential nonspecific uptake, we exposed radiolabeled (iodinated and Indium-111 labeled) preparations of monoclonal antibodies to a suspension of fresh liver and spleen cells at physiological temperature and compared their immunoreactivity, in vivo biodistribution, and tumor targeting to those of the same radiolabeled proteins without prior adsorption to this suspension. The biodistribution studies were performed under conditions of high background activity, i.e., shortly after the injection (1 hour) and using a high dose of the protein. Preadsorption of radiolabeled monoclonal antibodies results in a significant decreased uptake in certain normal tissues, i.e., greater contrast between normal and tumor tissues, as demonstrated by the quotient of the two target-to-nontarget ratios (exposed/unexposed antibody) which was greater than one for most of the tissues examined.
van den Abbeele
A D
AD
Department of Radiology (Nuclear Medicine), Harvard Medical School, Boston, Massachusetts.
Aaronson
R A
RA
Taube
R A
RA
Adelstein
S J
SJ
Kassis
A I
AI
D000327:Adsorption; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism*; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes