1. Development of [ 18 F]DASA-10 for enhanced imaging of pyruvate kinase M2.
- Author
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Kendirli MT, Malek R, Silveira MB, Acosta C, Zhang S, Azevedo C, Nagy SC, Habte F, James ML, Recht LD, and Beinat C
- Subjects
- Mice, Humans, Rats, Animals, HeLa Cells, Mice, Nude, Tissue Distribution, RNA, Small Interfering metabolism, Pyruvate Kinase metabolism, Glioma diagnostic imaging
- Abstract
Purpose: The aim of this study was to develop a positron emission tomography (PET) radiotracer for measuring pyruvate kinase M2 (PKM2) with improved physicochemical and pharmacokinetic properties compared to [
18 F]DASA-23., Experimental Design: First, we synthesized [18 F]DASA-10 and tested its uptake and retention compared to [18 F]DASA-23 in human and mouse glioma cell lines. We then confirmed the specificity of [18 F]DASA-10 by transiently modulating the expression of PKM2 in DU145 and HeLa cells. Next, we determined [18 F]DASA-10 pharmacokinetics in healthy nude mice using PET imaging and subsequently assessed the ability of [18 F]DASA-10 versus [18 F]DASA-23 to enable in vivo detection of intracranial gliomas in syngeneic C6 rat models of glioma., Results: [18 F]DASA-10 demonstrated excellent cellular uptake and retention with values significantly higher than [18 F]DASA-23 in all cell lines and timepoints investigated. [18 F]DASA-10 showed a 73 % and 65 % reduced uptake respectively in DU145 and HeLa cells treated with PKM2 siRNA as compared to control siRNA treated cells. [18 F]DASA-10 showed favorable biodistribution and pharmacokinetic properties and a significantly improved tumor-to-brain ratio in rat C6 glioma models relative to [18 F]DASA-23 (3.2 ± 0.8 versus 1.6 ± 0.3, p = 0.01)., Conclusion: [18 F]DASA-10 is a new PET radiotracer for molecular imaging of PKM2 with potential to overcome the prior limitations observed with [18 F]DASA-23. [18 F]DASA-10 shows promise for clinical translation to enable imaging of brain malignancies owing to its low background signal in the healthy brain., Competing Interests: Declaration of competing interest CB and MLJ hold a patent (US20180043040A1) describing the use of radiopharmaceuticals to measure PKM2. The authors declare no other conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)- Published
- 2023
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