In vivo quantitative assessment of therapeutic response to bortezomib therapy in disseminated animal models of multiple myeloma with [(18)F]FDG and [(64)Cu]Cu-LLP2A PET

BACKGROUND: Multiple myeloma (MM) is a disease of cancerous plasma cells in the bone marrow. Imaging-based timely determination of therapeutic response is critical for improving outcomes in MM patients. Very late antigen-4 (VLA4, CD49d/CD29) is overexpressed in MM cells. Here, we evaluated [(18)F]FDG and VLA4 targeted [(64)Cu]Cu-LLP2A for quantitative PET imaging in disseminated MM models of variable VLA4 expression, following bortezomib therapy. METHODS: In vitro and ex vivo VLA4 expression was evaluated by flow cytometry. Human MM cells, MM.1S-CG and U266-CG (C: luciferase and G: green fluorescent protein), were injected intravenously in NOD-SCID gamma mice. Tumor progression was monitored by bioluminescence imaging (BLI). Treatment group received bortezomib (1 mg/kg, twice/week) intraperitoneally. All cohorts (treated, untreated and no tumor) were longitudinally imaged with [(18)F]FDG (7.4–8.0 MBq) and [(64)Cu]Cu-LLP2A (2–3 MBq; Molar Activity: 44.14 ± 1.40 MBq/nmol) PET, respectively. RESULTS: Flow cytometry confirmed high expression of CD49d in U266 cells (> 99%) and moderate expression in MM.1S cells (~ 52%). BLI showed decrease in total body flux in treated mice. In MM.1S-CG untreated versus treated mice, [(64)Cu]Cu-LLP2A localized with a significantly higher SUV(mean) in spine (0.58 versus 0.31, p < 0.01) and femur (0.72 versus 0.39, p < 0.05) at week 4 post-tumor inoculation. There was a four-fold higher uptake of [(64)Cu]Cu-LLP2A (SUV(mean)) in untreated U266-CG mice compared to treated mice at 3 weeks post-treatment. Compared to [(64)Cu]Cu-LLP2A, [(18)F]FDG PET detected treatment-related changes at later time points. CONCLUSION: [(64)Cu]Cu-LLP2A is a promising tracer for timely in vivo assessment of therapeutic response in disseminated models of MM. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13550-021-00840-4.