Comparative evaluation of 18F-FGln and 18F-FDG PET imaging in neuroblastoma in vitro and in vivo

Purpose: The aim of our study was to compare glutamine analog 4-18F-(2S,4R)-fluoroglutamine (18F-FGln) positron emission tomography (PET) imaging with 18F-fluorodeoxyglucose (18F-FDG) imaging in diagnosis of neuroblastoma. Methods:In this study, MYCN amplification neuroblastoma was found to be more addicted to glutamine relied on ASCT2 in vitro cell uptake and in vivo mice models. Cell uptake studies and small-animal PET studies of 18F-FGln and 18F-FDG were conducted in MYCN amplification and non- MYCN amplification cells and animal models. In addition, knockdown of ASCT2(SLC1A5) in MYCN amplification cell and xenografts were studied using 18F-FGln. Western blot (WB), real-time polymerase chain reaction (RT-PCR) or immunofluorescence (IF) assays were used to evaluate the prevalence of ASCT2.

Results: MYCN amplification cells showed a high glutamine uptake in vitro studies and a higher uptake than in surrounding muscle tissues and the maximum uptake than that in non-MYCN amplification tumor in vivo study. ShRNA knockdown of ASCT2 in MYCN amplification cell xenografts significantly inhibited tumor uptake of glutamine and growth, suggesting that MYCN amplification neuroblastoma may use more glutamine for energy production relied on activation of ASCT2. Conclusion: 18F-FGln PET imaging may provide a supplementary tool in the diagnosis of MYCN amplification neuroblastoma comparing to 18F-FDG. ASCT2 is the key glutamine transporter that regulates neuroblastoma proliferation and metabolism.