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The Utility of [18F]DASA-23 for Molecular Imaging of Prostate Cancer with Positron Emission Tomography

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Abstract

Purpose

There is a strong, unmet need for superior positron emission tomography (PET) imaging agents that are able to measure biochemical processes specific to prostate cancer. Pyruvate kinase M2 (PKM2) catalyzes the concluding step in glycolysis and is a key regulator of tumor growth and metabolism. Elevation of PKM2 expression was detected in Gleason 8–10 tumors compared to Gleason 6–7 carcinomas, indicating that PKM2 may potentially be a marker of aggressive prostate cancer. We have recently reported the development of a PKM2-specific radiopharmaceutical [18F]DASA-23 and herein describe its evaluation in cell culture and preclinical models of prostate cancer.

Procedure

The cellular uptake of [18F]DASA-23 was evaluated in a panel of prostate cancer cell lines and compared to that of [18F]FDG. The specificity of [18F]DASA-23 to measure PKM2 levels in cell culture was additionally confirmed through the use of PKM2-specific siRNA. PET imaging studies were then completed utilizing subcutaneous prostate cancer xenografts using either PC3 or DU145 cells in mice.

Results

[18F]DASA-23 uptake values over 60-min incubation period in PC3, LnCAP, and DU145 respectively were 23.4 ± 4.5, 18.0 ± 2.1, and 53.1 ± 4.6 % tracer/mg protein. Transient reduction in PKM2 protein expression with siRNA resulted in a 50.1 % reduction in radiotracer uptake in DU145 cells. Small animal PET imaging revealed 0.86 ± 0.13 and 1.6 ± 0.2 % ID/g at 30 min post injection of radioactivity in DU145 and PC3 subcutaneous tumor bearing mice respectively.

Conclusion

Herein, we evaluated a F-18-labeled PKM2-specific radiotracer, [18F]DASA-23, for the molecular imaging of prostate cancer with PET. [18F]DASA-23 revealed rapid and extensive uptake levels in cellular uptake studies of prostate cancer cells; however, there was only modest tumor uptake when evaluated in mouse subcutaneous tumor models.

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Acknowledgements

We thank the Radiochemistry Facility at Stanford University for the 18F-18 production in particular Drs. Bin Shen and Jun Hyung Park. We would also like to thank the Small Animal Imaging Facility at Stanford, particularly Dr. Timothy Doyle.

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Authors and Affiliations

  1. Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA, 943065, USA

    Corinne Beinat, Tom Haywood, Yun-Sheng Chen, Chirag B. Patel, Israt S. Alam, Surya Murty & Sanjiv Sam Gambhir

  2. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Chirag B. Patel

  3. Department of Bioengineering and Materials Science & Engineering, Bio-X, Stanford University, Stanford, CA, 94305, USA

    Surya Murty & Sanjiv Sam Gambhir

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  1. Corinne Beinat
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Correspondence to Sanjiv Sam Gambhir.

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Beinat, C., Haywood, T., Chen, YS. et al. The Utility of [18F]DASA-23 for Molecular Imaging of Prostate Cancer with Positron Emission Tomography. Mol Imaging Biol 20, 1015–1024 (2018). https://doi.org/10.1007/s11307-018-1194-y

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