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[18F](2S,4R)-4-Fluoroglutamine as a New Positron Emission Tomography Tracer in Myeloma
- 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.
- Subjects :
- Cancer Research
glutamine
metabolism
mouse model
myeloma
nuclear medicine
positron-emission tomography
In vivo
medicine
RC254-282
Multiple myeloma
medicine.diagnostic_test
Chemistry
Bortezomib
business.industry
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
Glutamine
medicine.anatomical_structure
Oncology
Cell culture
Positron emission tomography
Proteasome inhibitor
Bone marrow
Nuclear medicine
business
medicine.drug
Subjects
Details
- ISSN :
- 2234943X
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Frontiers in Oncology
- Accession number :
- edsair.doi.dedup.....e56becb7359fad97eda888d0a63a0873