9 research outputs found
Tumor Targeting by a Multivalent Single-Chain Fv (scFv) Anti-Lewis Y Antibody Construct
The use of single-chain variable fragment (scFv) constructs has been investigated in cancer radioimmunotherapy (RIT) and radioimmunodetection, as these molecules permit rapid tumor penetration and clearance from the serum relative to whole IgG. Multimerization of scFv constructs has demonstrated improvements in functional affinity (i.e., avidity) and maximal tumor uptake. In this paper, we report the first biodistribution and pharmacokinetics studies of a noncovalent, direct-linked scFv (VL-0-VH) trimeric/tetrameric âmultimerâ of the anti-Lewis Y monoclonal antibody, hu3S193. The in vitro binding and in vivo biodistribution of the hu3S193 multimer was characterized alongside the hu3S193 F(abâ˛)2 following radiolabeling with the Indium-111 (111In) radioisotope. Immunoreactivities of the radiolabeled multimer and F(abâ˛)2 were 73% and 53.2%, and binding affinities (Ka) were 1.58 Ă 107 Mâ1 and 4.31 Ă 106 Mâ1 for the multimer and F(abâ˛)2, respectively. Maximal tumor uptake in Ley-positive MCF-7 breast cancer xenografted BALB/c nude mice was 12.6 Âą 2.5 percent injected dose/per gram (%ID/g) at 6 hours postinjection for the multimer and 15.7 Âą 2.1 %ID/g at 24 hours postinjection for the F(abâ˛)2. However, limited in vitro stability and high renal localization of radiolabeled constructs were observed, which, despite the observed tumor targeting of the hu3S193 multimer, most likely preclude its use in RIT and imaging modalities