Bavituximab is a chimeric
monoclonal antibody with immune modulating and
tumor-associated vascular disrupting properties demonstrated in models of
non-small cell lung cancer (NSCLC). The molecular target of
Bavituximab,
phosphatidylserine (PS), is exposed on the outer leaflet of the membrane bi-layer of malignant vascular endothelial cells and
tumor cells to a greater extent than on normal tissues. We evaluated the
tumor-targeting properties of
Bavituximab for imaging of NSCLC xenografts when radiolabeled with (111)In through conjugation with a bifunctional
chelating agent,
1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (
DOTA). In vitro binding of (111)In-DOTA-Bavituximab to PS was determined by
enzyme-linked
immunosorbent assay (ELISA). Biodistribution of (111)In-DOTA-Bavituximab was conducted in normal rats, which provided data for dosimetry calculation. Single-photon emission computed tomography/computed tomography (SPECT/CT) imaging was performed in athymic nude rats bearing A549 NSCLC xenografts. At the molar conjugation ratio of 0.54
DOTA per
Bavituximab, the PS binding affinity of (111)In-DOTA-Bavituximab was comparable to that of unmodified
Bavituximab. Based on the quantitative SPECT/CT imaging data analysis, (111)In-DOTA-Bavituximab demonstrated
tumor-specific uptake as measured by the
tumor-tomuscle ratio, which peaked at 5.2 at 72 hr post-injection. In contrast, the control antibody only presented a contrast of 1.2 at the same time point.These findings may underlie the diagnostic efficacy and relative low rates of systemic vascular and immune-related toxicities of this
immunoconjugate. Future applications of (111)In-DOTA-bavituximab may include prediction of efficacy, indication of
tumor immunologic status, or characterization of radiographic findings.