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

Mol Imaging Biol. 2018 Dec;20(6):1015-1024. doi: 10.1007/s11307-018-1194-y.

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.

Keywords: Positron emission tomography; Prostate cancer; Pyruvate kinase M2; Tumor glycolysis; [18F]DASA-23.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Diazonium Compounds / chemistry*
  • Diazonium Compounds / pharmacokinetics
  • Female
  • Fluorodeoxyglucose F18 / chemistry*
  • Fluorodeoxyglucose F18 / pharmacokinetics
  • Glycolysis / physiology
  • Heterografts
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Molecular Imaging / methods*
  • Neoplasm Transplantation
  • PC-3 Cells
  • Positron-Emission Tomography / methods*
  • Predictive Value of Tests
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Sulfanilic Acids / chemistry*
  • Sulfanilic Acids / pharmacokinetics

Substances

  • Diazonium Compounds
  • Sulfanilic Acids
  • Fluorodeoxyglucose F18
  • diazobenzenesulfonic acid