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[(18)F](2S,4R)-4-Fluoroglutamine as a New Positron Emission Tomography Tracer in Myeloma

The high glycolytic activity of multiple myeloma (MM) cells is the rationale for use of Positron Emission Tomography (PET) with (18)F-fluorodeoxyglucose ([(18)F]FDG) to detect both bone marrow (BM) and extramedullary disease. However, new tracers are actively searched because [(18)F]FDG-PET has some...

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Detalles Bibliográficos
Autores principales: Valtorta, Silvia, Toscani, Denise, Chiu, Martina, Sartori, Andrea, Coliva, Angela, Brevi, Arianna, Taurino, Giuseppe, Grioni, Matteo, Ruffini, Livia, Vacondio, Federica, Zanardi, Franca, Bellone, Matteo, Moresco, Rosa Maria, Bussolati, Ovidio, Giuliani, Nicola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546185/
https://www.ncbi.nlm.nih.gov/pubmed/34712616
http://dx.doi.org/10.3389/fonc.2021.760732
Descripción
Sumario:The high glycolytic activity of multiple myeloma (MM) cells is the rationale for use of Positron Emission Tomography (PET) with (18)F-fluorodeoxyglucose ([(18)F]FDG) to detect both bone marrow (BM) and extramedullary disease. However, new tracers are actively searched because [(18)F]FDG-PET has some limitations and there is a portion of MM patients who are negative. Glutamine (Gln) addiction has been recently described as a typical metabolic feature of MM cells. Yet, the possible exploitation of Gln as a PET tracer in MM has never been assessed so far and is investigated in this study in preclinical models. Firstly, we have synthesized enantiopure (2S,4R)-4-fluoroglutamine (4-FGln) and validated it as a Gln transport analogue in human MM cell lines, comparing its uptake with that of (3)H-labelled Gln. We then radiosynthesized [(18)F]4-FGln, tested its uptake in two different in vivo murine MM models, and checked the effect of Bortezomib, a proteasome inhibitor currently used in the treatment of MM. Both [(18)F]4-FGln and [(18)F]FDG clearly identified the spleen as site of MM cell colonization in C57BL/6 mice, challenged with syngeneic Vk12598 cells and assessed by PET. NOD.SCID mice, subcutaneously injected with human MM JJN3 cells, showed high values of both [(18)F]4-FGln and [(18)F]FDG uptake. Bortezomib significantly reduced the uptake of both radiopharmaceuticals in comparison with vehicle at post treatment PET. However, a reduction of glutaminolytic, but not of glycolytic, tumor volume was evident in mice showing the highest response to Bortezomib. Our data indicate that [(18)F](2S,4R)-4-FGln is a new PET tracer in preclinical MM models, yielding a rationale to design studies in MM patients.