RADIOPHARMACOLOGY 

The Quarterly Journal of Nuclear Medicine 2000 September;44(3):284-95

Copyright © 2009 EDIZIONI MINERVA MEDICA

language: English

Antibody phage display applications for nuclear medicine imaging and therapy

Winthrop M. D., Denardo G. L., Denardo S. J.

From the Department of Internal Medicine Division of Radiodiagnosis and Therapy University of California Davis Medical Center, Sacramento, CA, USA

Antibody-­based con­structs genet­i­cal­ly engi­neered ­from ­genes of ­diverse ori­gin pro­vide a remark­able oppor­tu­nity to devel­op func­tion­al molec­u­lar imag­ing tech­niques and spe­cif­ic molec­u­lar tar­get­ed radio­nu­clide ther­a­pies. Phage dis­play librar­ies of anti­body frag­ment ­genes can be ­used to ­select anti­body-­based con­structs ­that ­bind any cho­sen epi­tope. A ­large ­naive ­human anti­body-­based ­library was ­used to illus­trate bind­ing of anti­body con­structs to a varie­ty of com­mon and ­unique anti­gens. Antibody-­based librar­ies ­from hybrid­o­ma ­cells, lym­pho­cytes ­from immu­nized ­humans or ­from ­mice and ­human anti­body rep­er­toires pro­duced in trans­gen­ic ­mice ­have ­also ­been ­described. Several ­orders of mag­ni­tude of affin­ity enhance­ment can be ­achieved by ran­dom or ­site spe­cif­ic muta­tions of the select­ed bind­ing pep­tide ­domains of the scFv. Affinities (Kd) as ­high as 10-11 M (10 pM) for affin­ity-­matured scFv ­have ­been doc­u­ment­ed. Such ­gene librar­ies ­thus ­offer an ­almost lim­it­less varie­ty of anti­body-­based molec­u­lar bind­ing pep­tide mod­ules ­that can be ­used in crea­tive ­ways for the con­struc­tion of new tar­get­ing ­agents for func­tion­al or molec­u­lar imag­ing and ther­a­py.