Homodimerization of erythropoietin receptor by a bivalent monoclonal antibody triggers cell proliferation and differentiation of erythroid precursors.

Erythropoietin (EPO) stimulates proliferation and differentiation of erythroid progenitor cells. Several lines of evidence indicate that the most likely mechanism of EPO receptor (EPO-R) activation by EPO is homodimerization of the receptor on the surface of erythrocyte precursors. Therefore, we argued that it should be possible to raise EPO-R monoclonal antibodies (MoAbs) that would activate the receptor by dimerization and thus mimic EPO action.

Pharmacokinetics of pretargeted monoclonal antibody 2D12.5 and 88Y-Janus-2-(p-nitrobenzyl)-1,4,7,10-tetraazacyclododecanetetraacetic acid (DOTA) in BALB/c mice with KHJJ mouse adenocarcinoma: a model for 90Y radioimmunotherapy.

Three-step pretargeting for radioimmunotherapy in BALB/c mice with KHJJ tumors was done with monoclonal antibody (mAb) 2D12.5, which is specific for yttrium-1,4,7,10-tetraazacyclododecanetetraacetic acid (DOTA) but nonspecific for the tumor. Tumor uptake was by passive diffusion of mAb through leaky neovasculature in the tumor.

In vitro evaluation of white blood cell labelling with 99Tcm radiopharmaceuticals.

Several commercially available 99Tcm radiopharmaceuticals were tested as possible white blood cell labelling agents. Labelling efficiency, labelling stability and white blood cell adherence were measured in vitro. White blood cells were not successfully labelled with mebrofenin, disofenin, gluceptate or dimercaptosuccinic acid but were successfully labelled with exametazime, albumin colloid, sulphur colloid, sestamibi and teboroxime.

Immunogenicity in rabbits and mice of an antibody-chelate conjugate: comparison of (S) and (R) macrocyclic enantiomers and an acyclic chelating agent.

The macrocyclic bifunctional chelating agent 2-(p-bromoacetamidobenzyl)-1,4,7,10-tetraazacyclododecanetetraa cetic acid (BAD), forms inert metal complexes ideal for radioimmunotherapy. Kosmas et al. (Cancer Res.

Pretargeted immunoscintigraphy: effect of hapten valency on murine tumor uptake.

A method of radioimmunoscintigraphy using bivalent "Janus" haptens with an apparent enhanced affinity ("avidity") for the antibody is described. Janus with 50 micrograms pretargeted Mab WC3A11 resulted in significantly higher murine tumor concentrations (approximately 7%/g) compared to monovalent haptens (approximately 1.4%/g, p < 0.