[18F]Fluoro-DCP, a first generation PET radiotracer for monitoring protein sulfenylation in vivo
Kiran Kumar Solingapuram Sai,
Xiaofei Chen,
Zhe Li,
Caigang Zhu,
Kirtikar Shukla,
Tom E. Forshaw,
Hanzhi Wu,
Stephen A. Vance,
Buddhika Liyana Pathirannahel,
Megan Madonna,
Mark W. Dewhirst,
Allen W. Tsang,
Leslie B. Poole,
Nimmi Ramanujam,
S. Bruce King,
Cristina M. Furdui
Affiliations
Kiran Kumar Solingapuram Sai
Department of Radiology, Wake Forest School of Medicine, Winston‐Salem, North Carolina, USA
Xiaofei Chen
Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
Zhe Li
Department of Chemistry, Wake Forest University, Winston-Salem, North Carolina, USA
Caigang Zhu
Department of Biomedical Engineering, Duke University, Durham, NC, USA
Kirtikar Shukla
Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
Tom E. Forshaw
Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
Hanzhi Wu
Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
Stephen A. Vance
Department of Chemistry, Wake Forest University, Winston-Salem, North Carolina, USA
Buddhika Liyana Pathirannahel
Department of Radiology, Wake Forest School of Medicine, Winston‐Salem, North Carolina, USA
Megan Madonna
Department of Biomedical Engineering, Duke University, Durham, NC, USA
Mark W. Dewhirst
Department of Radiation Oncology, Duke University, Durham, NC, USA
Allen W. Tsang
Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
Leslie B. Poole
Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
Nimmi Ramanujam
Department of Biomedical Engineering, Duke University, Durham, NC, USA
S. Bruce King
Department of Chemistry, Wake Forest University, Winston-Salem, North Carolina, USA
Cristina M. Furdui
Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA; Corresponding author.
Redox metabolism plays essential functions in the pathology of cancer and many other diseases. While several radiotracers for imaging redox metabolism have been developed, there are no reports of radiotracers for in vivo imaging of protein oxidation. Here we take the first step towards this goal and describe the synthesis and kinetic properties of a new positron emission tomography (PET) [18F]Fluoro-DCP radiotracer for in vivo imaging of protein sulfenylation. Time course biodistribution and PET/CT studies using xenograft animal models of Head and Neck Squamous Cell Cancer (HNSCC) demonstrate its capability to distinguish between tumors with radiation sensitive and resistant phenotypes consistent with previous reports of decreased protein sulfenylation in clinical specimens of radiation resistant HNSCC. We envision further development of this technology to aid research efforts towards improving diagnosis of patients with radiation resistant tumors.
