P-016: The role [18F]-(2S,4R)-4-Fluoroglutamine as a new positron emission tomography tracer in Myeloma in vivo models.

Abstract

<h3>Background</h3> The high glycolytic activity of multiple myeloma (MM) cells is the rationale for use of Positron Emission Tomography (PET) with 18F-fluorodeoxyglucose ([18F]FDG) to detect both bone marrow (BM) and extramedullary disease. However, FDG-PET has some limitations, since there is a portion of MM patients who are negative, and new tracers are actively searched. Glutamine (Gln) addiction has been recently described as a peculiar metabolic feature of MM cells. Yet, the possible exploitation of Gln as a PET tracer in MM has never been assessed thus far and is investigated in this study. <h3>Methods</h3> We have firstly 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 3H-labelled Gln. We then radiosynthesized of [18F]4-FGln and tested its uptake for MM detection by PET in two different murine models and we checked the effect of Bortezomib treatment. <h3>Results</h3> Both [18F]4-FGln and [18F]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 [18F]4-FGln and [18F]FDG uptake to T/M: 2.3 ± 0.3 and 7.1 ± 2.6, respectively. With both [18F]4-FGln and [18F]FDG radiotracers, BOR treated animals displayed Standard Uptake Values (SUV) mean values significantly lower than controls at post treatment PET. However, [18F]4-FGln better correlated with the tumour volume in NOD.SCID mice, and a reduction of glutaminolytic, but not of glycolytic, tumour volume was evident in mice showing the highest response to Bortezomib. <h3>Conclusion</h3> Our data indicate that [18F](2S,4R)-4-FGln is a new PET tracer in pre-clinical MM models, yielding a rationale to design studies in MM patients.