CBMT-08. COMPARISON OF THREE METABOLIC PET RADIOTRACERS IN GLIOBLASTOMA: CELL CULTURE AND ANIMAL STUDIES. (5th November 2018)

• Record Type: Journal Article
• Authors: Beinat, Corinne; Patel, Chirag; Murty, Surya; Haywood, Tom; Hyung Park, Jun; Xie, Yuanyang; Gambhir, Sanjiv
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 6
• Page Start: vi34
• Page End: vi34
• Publication Date: 2018-11-05
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy148.127
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: INTRODUCTION: Positron emission tomography (PET) is a non-invasive imaging modality used to visualize and define tumors based on their molecular characteristics and may play an important role in diagnosis and response assessment in glioblastoma patients. We have reported [18F]DASA-23 as a novel radiotracer for the measurement of aberrantly-expressed pyruvate kinase M2 (PKM2) in glioblastoma. PKM2 represents an attractive target for PET imaging due to lack of expression in the healthy brain and key role in the glycolytic reprogramming of glioblastoma. METHODS: We compared the uptake dynamics and in vivo performance of [18F]DASA-23 to that of established radiotracers ([18F]FDG and [18F]FDOPA). Human U87 glioblastoma cells were studied for the uptake experiments and were also orthotopically implanted into nude mice (N=4) for in vivo microPET/CT dynamic imaging with the three radiotracers. Finally, a separate cohort of mice (N=6) was evaluated with [18F]DASA-23 microPET/CT before and one week post-initiation of vehicle or temozolomide chemotherapy (70 mg/kg, oral, 5 days per 28-day cycle). Data are reported as mean±SD. RESULTS: The cellular uptake at 60 minutes post-addition of radioactivity was 10.5 ± 0.5 %uptake/mg protein for [18F]DASA-23, which was significantly greater than that of [18F]FDG (1.94 ± 0.1, p<0.0001) and [18F]FDOPA (1.2 ± 0.1, p<0.0001). In the animal imaging studies at 30 minutes post-injection of radioactivity, [18F]DASA-23 clearly delineated the tumors from the surrounding healthy brain tissue and had a significantly higher tumor-to-brain ratio compared to that of [18F]FDG and [18F]FDOPA (4.1 ± 0.4 vs. 1.2 ± 0.2 [p=0.0005] and 2.6 ± 0.2 [p<0.0001], respectively). In another cohort of mice, the percent change in the [18F]DASA-23 tumor-to-brain ratio from pre-treatment to one week post-treatment was significantly reduced in the temozolomide compared to the vehicle group (p=0.004). CONCLUSIONS: These studies highlight the benefit of PET imaging with [18F]DASA-23 over other radiotracers ([18F]FDG and [18F]FDOPA) and suggest the potential to detect early response to temozolomide therapy with [18F]DASA-23.