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

Authors :
Silvia Valtorta
Denise Toscani
Martina Chiu
Andrea Sartori
Angela Coliva
Arianna Brevi
Giuseppe Taurino
Matteo Grioni
Livia Ruffini
Federica Vacondio
Franca Zanardi
Matteo Bellone
Rosa Maria Moresco
Ovidio Bussolati
Nicola Giuliani
Valtorta, S
Toscani, D
Chiu, M
Sartori, A
Coliva, A
Brevi, A
Taurino, G
Grioni, M
Ruffini, L
Vacondio, F
Zanardi, F
Bellone, M
Moresco, R
Bussolati, O
Giuliani, N
Source :
Frontiers in oncology 11 (2021): 760732. doi:10.3389/fonc.2021.760732, info:cnr-pdr/source/autori:Valtorta S.; Toscani D.; Chiu M.; Sartori A.; Coliva A.; Brevi A.; Taurino G.; Grioni M.; Ruffini L.; Vacondio F.; Zanardi F.; Bellone M.; Moresco R.M.; Bussolati O.; Giuliani N./titolo:[18F](2S,4R)-4-Fluoroglutamine as a New Positron Emission Tomography Tracer in Myeloma/doi:10.3389%2Ffonc.2021.760732/rivista:Frontiers in oncology/anno:2021/pagina_da:760732/pagina_a:/intervallo_pagine:760732/volume:11, Frontiers in Oncology, Vol 11 (2021)
Publication Year :
2021
Publisher :
Frontiers Media SA, 2021.

Abstract

The high glycolytic activity of multiple myeloma (MM) cells is the rationale for use of Positron Emission Tomography (PET) with18F-fluorodeoxyglucose ([18F]FDG) to detect both bone marrow (BM) and extramedullary disease. However, new tracers are actively searched because [18F]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 of3H-labelled Gln. We then radiosynthesized [18F]4-FGln, tested its uptake in two differentin vivomurine MM models, and checked the effect of Bortezomib, a proteasome inhibitor currently used in the treatment of MM. 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. 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 [18F](2S,4R)-4-FGln is a new PET tracer in preclinical MM models, yielding a rationale to design studies in MM patients.

Details

ISSN :
2234943X
Volume :
11
Database :
OpenAIRE
Journal :
Frontiers in Oncology
Accession number :
edsair.doi.dedup.....e56becb7359fad97eda888d0a63a0873