TY - JOUR T1 - [18F](2S,4R)4-Fluoroglutamine PET Detects Changes in Glutamine Pool in Triple Negative Breast Cancer in Response to Glutaminase Inhibition JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1363 LP - 1363 VL - 57 IS - supplement 2 AU - Rong Zhou AU - Brian Lieberman AU - Shihong Li AU - Karl Ploessl AU - Hoon Choi AU - Eric Blankemeyer AU - Sharon Lee AU - Austin Pantel AU - Hank Kung AU - Robert Mach AU - David Mankoff Y1 - 2016/05/01 UR - http://jnm.snmjournals.org/content/57/supplement_2/1363.abstract N2 - 1363Objectives -Methods Mice bearing human TNBC (HCC1806) or receptor positive breast cancer (MCF-7) xenografts undergo [18F]Fluoroglutamine PET imaging before and after treatment with glutaminase inhibitors or vehicle solution. Metabolic conversion of [18F]Fluoroglutamine to [18F]Fluoroglutamate in the tumor and blood was analyzed. Tumor glutamine pool (µmole/gram) was estimated by high resolution proton magnetic resonance spectroscopy (1H MRS) of aqueous metabolites extracted from tumor homogenates. Tumor-to-blood-activity-ratios (T/B) derived from [18F]Fluoroglutamine PET images were compared between GLS inhibitor vs. vehicle treated mice and were correlated with tumor glutamine pool size quantified by independent 1H MRS.Results HCC1806 cells and tumors, due to high GLS activity, exhibit low cellular glutamine concentration, which was markedly increased after GLS inhibition. In contrast, glutamine concentration was much higher and exhibited little change upon GLS inhibition in MCF-7 tumor, whose GLS activity is inherently low. Minimal metabolic conversion of [18F]Fluoroglutamine to [18F]Fluoroglutamate was identified in the blood and tumor regardless treatment by GLS inhibitor or vehicle, suggesting [18F]Fluoroglutamine (parent tracer) is the major species in blood and tumor within the time frame of PET imaging. In mice bearing TNBC tumors, T/B values increased significantly in response to GLS inhibition, whereas no change was induced by vehicle treatment. In receptor-positive tumors, however, GLS inhibitor was not able to induce changes in T/B ratio. Furthermore, in HCC1806 and MCF-7 tumors after glutaminase inhibitor or vehicle treatment, a positive correlation between T/B values (obtained from PET) versus glutamine concentrations (by MRS) was identified (R2=0.8). Finally, glutamine distribution volume (DV), which provides an estimate of the glutamine pool size, has been obtained via compartment modeling of dynamic PET data and preliminary results are reported in a separate abstract.Conclusions breast cancers with high glutaminase activity, changes of cellular glutamine pool size in response to GLS inhibitor treatment can be detected by [18F]Fluoroglutamine PET. This biomarker may facilitate the development of this new category of cancer therapeutics. ER -