Positron emission tomography of sodium glucose cotransport activity in high grade astrocytomas

• Published in: Journal of neuro-oncology 2018-07, Vol.138 (3), p.557-569
• Main Authors: Kepe, Vladimir, Scafoglio, Claudio, Liu, Jie, Yong, William H., Bergsneider, Marvin, Huang, Sung-Cheng, Barrio, Jorge R., Wright, Ernest M.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Astrocytes; Astrocytoma; Astrocytoma - diagnostic imaging; Astrocytoma - metabolism; Astrocytoma - pathology; Brain - diagnostic imaging; Brain - metabolism; Brain - pathology; Brain Neoplasms - diagnostic imaging; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Clinical Study; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Endothelial cells; Endothelial Cells - metabolism; Endothelial Cells - pathology; Female; Glioblastoma; Glioblastoma cells; Glucose; Glucose transporter; Glucosides; Humans; Immunocytochemistry; Immunohistochemistry; Magnetic Resonance Imaging; Male; Medical imaging; Medicine; Medicine & Public Health; Microvasculature; Microvessels - metabolism; Microvessels - pathology; Middle Aged; Na+/glucose cotransporter; Neoplasm Grading; Neuroimaging; Neurology; NMR; Nuclear magnetic resonance; Oncology; Pancreas; Positron emission tomography; Preliminary Data; Prostate; Prostate cancer; Radiopharmaceuticals; Sodium; Sodium-Glucose Transporter 2 - metabolism; Tumors
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-018-2823-7

A novel glucose transporter, the sodium glucose cotransporter 2 (SGLT2), has been demonstrated to contribute to the demand for glucose by pancreatic and prostate tumors, and its functional activity has been imaged using a SGLT specific PET imaging probe, α-methyl-4-[F-18]fluoro-4-deoxy- d -glucopyaranoside (Me-4FDG). In this study, Me-4FDG PET was extended to evaluate patients with high-grade astrocytic tumors. Me-4FDG PET scans were performed in four patients diagnosed with WHO Grade III or IV astrocytomas and control subjects, and compared with 2-deoxy-2-[F-18]fluoro- d -glucose (2-FDG) PET and magnetic resonance imaging (MRI) of the same subjects. Immunocytochemistry was carried out on Grade IV astrocytomas to determine the cellular location of SGLT proteins within the tumors. Me-4FDG retention was pronounced in astrocytomas in dramatic contrast to the lack of uptake into the normal brain, resulting in a high signal-to-noise ratio. Macroscopically, the distribution of Me-4FDG within the tumors overlapped with that of 2-FDG uptake and tumor definition using contrast-enhanced MRI images. Microscopically, the SGLT2 protein was found to be expressed in neoplastic glioblastoma cells and endothelial cells of the proliferating microvasculature. This preliminary study shows that Me-4FDG is a highly sensitive probe for visualization of high-grade astrocytomas by PET. The distribution of Me-4FDG within tumors overlapped that for 2-FDG, but the absence of background brain Me-4FDG resulted in superior imaging sensitivity. Furthermore, the presence of SGLT2 protein in astrocytoma cells and the proliferating microvasculature may offer a novel therapy using the SGLT2 inhibitors already approved by the FDA to treat type 2 diabetes mellitus.