Glutamine metabolism as new marker and diagnostic tool for bone diseases in mm patients

Description

The rationale of this research translational project has been to investigate the role of glutamine (Gln) and glutamate metabolism as possible new diagnostic tools for MM bone disease in MM patients. The aims of the project were: -Firstly, to check how the alteration of Gln metabolisms induced by MM cells and consequently the Gln addicted features of MM cells affect both osteoblast (OB) and osteoclast (OC) differentiation and activity in vitro and in the development of bone disease. -To evaluate the Gln synthetase (GS) expression in MM bone microenvironment cells and to evaluate the effect of GS expression by MM cells on OB and OC differentiation. -To investigate the possible relationship between metabolic features of bone microenvironment and the presence of bone disease in MM patients. Gln, glutamate (Glu) and ammonium bone marrow (BM) levels will be assessed in MM patients and correlated with the presence of osteolytic lesions and the extension of bone disease. The role of Gln and GS in the MM bone microenvironment will be clarified thus providing novel metabolic biomarkers of bone disease and new strategies for the prevention of osteolytic lesions. -To assess [18F]4F-Gln-PET in different murine MM models in order to investigate the role of Gln as possible new marker of bone disease and to provide marked improvements in the imaging of bone disease and, potentially, in the management of MM patients -Finally, based of the preclinical data on [18F]4F-Gln-PET in mouse a clinical development program will be planned in MM patients to check the possible use of [18F]4F-Gln as new tracer for the imaging of bone disease in MM patients in comparison with standard FDG.