In vivo labelling of biotinylated monoclonal antibodies by radioactive avidin: a strategy to increase tumor radiolocalization.
Several monoclonal antibodies (MAbs), reactive with tumor-associated antigens, selectively persist on tumor sites in vivo for many days. If biotinylated, such highly specific tags on tumor cells could become targets for radioactive avidin, administered after suitable intervals. The proposed strategy is based on a number of assumptions concerning the ability of avidin to preserve its biological properties in heterologous in vivo environments, on its lack of toxicity and on its biodistribution. A preliminary study has been carried out in rabbits, using biotinylated nitrocellulose and polystyrene targets. The results of this study indicate that in rabbits 1) avidin can be administered i.v. and i.p. without adverse reactions, 2) it does not show any preferential localization, 3) it is eliminated with a biological half-life of 24 hr, 4) its biological properties are not impaired by in vivo conditions, since it accumulates at biotinylated targets only, 5) CEA-bearing targets can be biotinylated in vivo by biotin-labelled anti-CEA MAbs and 6) the biotin-avidin chain can be further extended in vivo since bound avidin is still able to bind biotinylated radioactive proteins.
Paganelli
G
G
Ospedale M. Bufalini, Corso Garibaldi, Cesena, Italy.
Riva
P
P
Deleide
G
G
Clivio
A
A
Chiolerio
F
F
Scassellati
G A
GA
Malcovati
M
M
Siccardi
A G
AG
D000818:Animals; D000911:Antibodies, Monoclonal; D001360:Avidin; D001710:Biotin; D002272:Carcinoembryonic Antigen / Q000032:analysis; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging*; D011817:Rabbits; D011877:Radionuclide Imaging; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D001360:Avidin; D001710:Biotin