Molecularly targeted imaging in multiple myeloma (Conference Presentation)

Introduction. Multiple myeloma (MM) is a cancer of terminally differentiated plasma B-cells that originates in the hematopoietic bone marrow and accounts for 15-20% of all hematologic malignancies. Combination therapies are commonly prescribed to patients with relapsed/refractory MM, which necessitates the stratification of responding patients to minimize toxicities and improve quality of life. Very late antigen-4 (VLA-4) and cluster of differentiation 38 (CD38) are over-expressed proteins on MM cells. Here, we will demonstrate VLA-4 and CD38 targeted molecular imaging as potential surrogates for targeted therapy. Materials and Methods: Daratumumab (Janssen Biotech), CD38 targeted antibody, was provided by the Siteman Cancer Center pharmacy. Sulfo-Cyanine5 (Cy5) NHS ester (Lumiprobe) was conjugated resulting in a 5:1 dye to antibody ratio. In vivo fluorescence imaging was performed on fox chase severe combined immunodeficient beige mice bearing MM1.S-GFP subcutaneous myeloma tumors (n = 7). VLA-4 imaging was performed using a highly selective peptidomimetic ligand (LLP2A) for the activated form of VLA-4 in 5TGM1-GFP syngeneic mouse model. Results and Conclusion. Here we used selective near-infrared fluorescent probes LLP2A-Cy5 and daratumumab-Cy5 to target α4β1 and CD38 expression respectively in vitro and in vivo in relevant myeloma models. Specificity for α4β1 over expressing cells was maintained in vivo in medullar MM with 7-fold and 2-fold increase in LLP2A-Cy5 uptake into tumor-bearing bone marrow and spleen, respectively. Tumor uptake of the fluorescently-labelled daratumumab increased through the imaging period with tumor to blood ratio 7 days post-contrast nearly doubling relative to pre-contrast. We are validating molecular imaging approaches for targeted therapy.