Posted: Tuesday, January 25, 2022
Silvia Valtorta, MD, of the University of Milan Bicocca, Milan, Italy, and colleagues found that [18-F]4-fluoroglutamine (4-FGln) appeared to identify multiple myeloma when human cells are injected in mice. Additionally, the authors proposed that this novel PET tracer can be used in preclinical multiple myeloma models, which also may help to design studies for patients with multiple myeloma. A detailed report of the study was published in the journal Frontiers of Oncology.
“Growing evidence suggests the possible use of 4-FGln as a new tracer in cancer patients taking advantage by the Gln-dependent metabolic profile of several tumors,” said the authors. “Moreover, 4-FGln could be used to study the metabolic profile and the Gln-dependent addiction of multiple myeloma cells in order to design a metabolic-based therapeutic approach.”
The study explored glutamine addiction as a typical metabolic feature of multiple myeloma cells in preclinical models in mice. First, researchers synthesized enantiopure 4-FGln and validated it as a glutamine transport analog in human multiple myeloma cell lines, comparing its uptake with that of 3 H–labelled glutamine. Then, the authors radiosynthesized 4-FGln, tested its uptake in two different in vivo murine multiple myeloma models, and checked the effect of the proteasome inhibitor bortezomib.
Results showed both 4-FGln and F-fluorodeoxyglucose (FDG) identified the spleen as the site of multiple myeloma cell colonization in C57BL/6 mice, challenged with syngeneic Vk12598 cells and assessed by PET. NOD.SCID mice, subcutaneously injected with human multiple myeloma JJN3 cells, showed high values of both 4-FGln and FDG uptake. Bortezomib appeared to significantly reduce the uptake of both radiopharmaceuticals in comparison with vehicle at post-treatment PET. However, reduction of glutaminolytic, but not of glycolytic, tumor volume was evident in mice showing the highest response to bortezomib.
Disclosure: For full disclosures of study authors, visit frontiersin.org.