Antibody phage display applications for nuclear medicine imaging and therapy.
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.
Winthrop
M D
MD
Department of Internal Medicine, University of California Davis Medical Center, Sacramento 95816, USA.
Denardo
G L
GL
Denardo
S J
SJ
D000818:Animals; D000906:Antibodies / Q000235:genetics*; D018033:Antibodies, Bispecific; D015723:Gene Library; D005818:Genetic Engineering; D006801:Humans; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy; D019151:Peptide Library; D016719:Radioimmunodetection; D016499:Radioimmunotherapy
D000906:Antibodies; D018033:Antibodies, Bispecific; D019151:Peptide Library