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      NIMG-36. EVALUATION OF [18F]DASA-23 FOR NON-INVASIVE MEASUREMENT OF ABERRANTLY EXPRESSED PYRUVATE KINASE M2 IN GLIOMA: FIRST-IN-HUMAN STUDY

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          Abstract

          OBJECTIVES

          We developed 1-((2-fluoro-6-(fluoro-[18F])phenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) as a novel radiopharmaceutical to measure pyruvate kinase M2 levels by positron emission tomography (PET). PKM2 catalyzes the final step in glycolysis, the key process of tumor metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in the healthy brain, making it an important biomarker of cancer glycolytic re-programming. Here, we report the first evaluation of [18F]DASA-23 in human healthy volunteers and subjects with low-grade (LGG) and high-grade glioma (HGG).

          METHODS

          [18F]DASA-23 was synthesized under GMP conditions. Brain [18F]DASA-23 PET/MRI scans (3T) were performed in human healthy volunteers (n=5) and subjects with LGG (n=3) and HGG (n=2). The PET imaging duration was 60 min and standardized uptake value (SUV) calculations were performed on the 30–60 min summed images. The maximum SUV in the tumor (TumorSUVmax) and contralateral white matter (WMSUVmax) were calculated.

          RESULTS

          [18F]DASA-23 specific activity was 2961±873 mCi/µmol (n=10) with radiochemical purity >95%, injected mass of 1.8±0.7 mcg, and dose of 0.3±0.02 mcg per kg body weight. In healthy volunteers, [18F]DASA-23 crossed the intact blood-brain barrier and was rapidly cleared through the bladder and also showed uptake in the gallbladder, liver, and intestines over time. [18F]DASA-23 was found to be intact in plasma up to 10 min post-injection and 75% intact at 30 min post-injection. In subjects with glioma, TumorSUVmax was significantly greater in HGG (2.2±0.4, n=2) compared to LGG (0.8±0.3m n=3), p=0.02. In this early human series, the normalized ratio of TumorSUVmax/WMSUVmax was not significantly different between subjects with HGG (2.0±0.6) and LGG (1.0±0.4), p=0.1.

          CONCLUSION

          [18F]DASA-23 is a promising new imaging agent for the non-invasive delineation of LGG and HGG based on aberrantly expressed PKM2. An ongoing study is evaluating the utility of this agent in additional patients with intracranial malignancies (NCT03539731).

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          Author and article information

          Journal
          Neuro Oncol
          Neuro-oncology
          neuonc
          Neuro-Oncology
          Oxford University Press (US )
          1522-8517
          1523-5866
          November 2019
          11 November 2019
          : 21
          : Suppl 6 , Abstracts from the 24th Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology November 22 – 24, 2019 Phoenix, Arizona
          : vi169
          Affiliations
          [1 ] Stanford University , Palo Alto, CA, USA
          [2 ] Stanford University , Stanford, CA, USA
          [3 ] Stanford School of Medicine , Stanford, CA, USA
          Article
          PMC6847186 PMC6847186 6847186 noz175.706
          10.1093/neuonc/noz175.706
          6847186
          b6f3df4d-5fd7-445f-8fcf-25a072e01e37
          © The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

          This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model ( https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

          History
          Page count
          Pages: 1
          Categories
          Neuro-Imaging

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