Molecular imaging of VEGF expression in multiple myeloma and non-Hodgkin Lymphoma

Abstract

Angiogenesis is a crucial process in the growth, development, and metastasis of many tumor types, including Non-Hodgkin’s lymphoma (NHL) and Multiple Myeloma (MM). Vascular endothelial growth factor (VEGF) overexpression is known to be associated with poor prognosis in both pathologies, representing a rational target for anti-angiogenic therapy in NHL and MM. The monoclonal antibody Bevacizumab binds to VEGF with high affinity and blocks its action. We aim to evaluate Bevacizumab as a potential radioactive and fluorescence agent for imaging VEGF expression in MM and NHL. Flow cytometry analysis revealed VEGF expression in MM and NHL cell lines is mainly intracellularly. Biodistribution and Single-photon emission computed tomography/computed tomography (SPECT/CT) studies of 99mTc-HYNICBevacizumab showed a slow blood clearance and supradiaphragmatic, head, axial and appendicular skeleton can be evaluated without much interference. Tumor-to-muscle ratio increased with time and is similar to the ones reported with other 99mTc radiolabeled antibodies. Cy7-Bevacizumab fluorescent imaging allowed MM and NHL tumor visualization with greater spatial resolution than SPECT/CT. We successfully synthesized 99mTc and Cy7-labeled anti-VEGF mAb (Bevacizumab) to be used to target VEGF expression in vivo in MM and LNH. Our encouraging results, although working with 99mTc, highlight the importance of radioinmuno-oncology as a potential tool to fight these diseases. Optical imaging of these tracers would enhance tumor sampling and guide surgical removal.