[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

doi:10.1016/j.redox.2021.102218

[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

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

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.

Original language	English
Article number	102218
Journal	Redox Biology
Volume	49
DOIs	https://doi.org/10.1016/j.redox.2021.102218
State	Published - Feb 2022

Bibliographical note

Publisher Copyright:
© 2021

Funding

The authors acknowledge financial support for these studies provided by the Center for Redox Biology and Medicine at Wake Forest School of Medicine (pilot funds to S.B.K.), the Wake Forest Baptist Comprehensive Cancer Center (NIH/NCI P30 CA12197 ; pilot funds to C.M.F. and support of shared resources facilities), NIH/NCI R42 CA156901 to N.R., and NIH/NIGMS R35 GM135179 to L.B.P..

Funders	Funder number
Center for Redox Biology and Medicine at Wake Forest School of Medicine
National Institutes of Health (NIH)
National Childhood Cancer Registry – National Cancer Institute	R42 CA156901, P30 CA12197
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences	R35GM135179
Comprehensive Cancer Center at Wake Forest Baptist Medical Center

Keywords

Head and Neck Squamous Cell Cancer
PET imaging
Protein sulfenylation
Radiation resistance
[18F]F-DCP

ASJC Scopus subject areas

Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.redox.2021.102218

Cite this

Solingapuram Sai, K. K., Chen, X., Li, Z., Zhu, C., Shukla, K., Forshaw, T. E., Wu, H., Vance, S. A., Pathirannahel, B. L., Madonna, M., Dewhirst, M. W., Tsang, A. W., Poole, L. B., Ramanujam, N., King, S. B., & Furdui, C. M. (2022). [¹⁸F]Fluoro-DCP, a first generation PET radiotracer for monitoring protein sulfenylation in vivo. Redox Biology, 49, Article 102218. https://doi.org/10.1016/j.redox.2021.102218

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abstract = "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.",

keywords = "Head and Neck Squamous Cell Cancer, PET imaging, Protein sulfenylation, Radiation resistance, [18F]F-DCP",

author = "\{Solingapuram Sai\}, \{Kiran Kumar\} and Xiaofei Chen and Zhe Li and Caigang Zhu and Kirtikar Shukla and Forshaw, \{Tom E.\} and Hanzhi Wu and Vance, \{Stephen A.\} and Pathirannahel, \{Buddhika Liyana\} and Megan Madonna and Dewhirst, \{Mark W.\} and Tsang, \{Allen W.\} and Poole, \{Leslie B.\} and Nimmi Ramanujam and King, \{S. Bruce\} and Furdui, \{Cristina M.\}",

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doi = "10.1016/j.redox.2021.102218",

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volume = "49",

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Solingapuram Sai, KK, Chen, X, Li, Z, Zhu, C, Shukla, K, Forshaw, TE, Wu, H, Vance, SA, Pathirannahel, BL, Madonna, M, Dewhirst, MW, Tsang, AW, Poole, LB, Ramanujam, N, King, SB & Furdui, CM 2022, '[¹⁸F]Fluoro-DCP, a first generation PET radiotracer for monitoring protein sulfenylation in vivo', Redox Biology, vol. 49, 102218. https://doi.org/10.1016/j.redox.2021.102218

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AU - Solingapuram Sai, Kiran Kumar

AU - Chen, Xiaofei

AU - Li, Zhe

AU - Zhu, Caigang

AU - Shukla, Kirtikar

AU - Forshaw, Tom E.

AU - Wu, Hanzhi

AU - Vance, Stephen A.

AU - Pathirannahel, Buddhika Liyana

AU - Madonna, Megan

AU - Dewhirst, Mark W.

AU - Tsang, Allen W.

AU - Poole, Leslie B.

AU - Ramanujam, Nimmi

AU - King, S. Bruce

AU - Furdui, Cristina M.

PY - 2022/2

Y1 - 2022/2

N2 - 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.

AB - 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.

KW - Head and Neck Squamous Cell Cancer

KW - PET imaging

KW - Protein sulfenylation

KW - Radiation resistance

KW - [18F]F-DCP

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