[18F]FSPG-PET provides an early marker of radiotherapy response in head and neck squamous cell cancer

Khrishanthne Sambasivan; Will E Tyrrell; Rizwan Farooq; Jenasee Mynerich; Richard S Edwards; Muhammet Tanc; Teresa Guerrero Urbano; Timothy H Witney

doi:10.1038/s44303-024-00038-y

[¹⁸F]FSPG-PET provides an early marker of radiotherapy response in head and neck squamous cell cancer

Khrishanthne Sambasivan, Will E Tyrrell, Rizwan Farooq, Jenasee Mynerich, Richard S Edwards, Muhammet Tanc, Teresa Guerrero Urbano, Timothy H Witney

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

Abstract

The ability to image early treatment response to radiotherapy in head and neck squamous cell carcinoma (HNSCC) will enable the identification of radioresistant tumor volumes suitable for treatment intensification. Here, we propose the system x c - radiotracer (4 S)-4-(3-[ 18F]fluoropropyl)-L-glutamate ([ 18F]FSPG) as a non-invasive method to monitor radiation response in HNSCC. We assessed temporal changes in cell death, antioxidant status, and [ 18F]FSPG retention following a single dose of 10 Gy irradiation in FaDU HNSCC cells. Next, using a fractionated course of radiotherapy, we assessed tumor volume changes and performed [ 18F]FSPG-PET imaging in FaDU-bearing mouse xenografts, followed by ex vivo response assessment. In cells, 10 Gy irradiation reduced [ 18F]FSPG retention, coinciding with the induction of apoptosis and the production of reactive oxygen species. In vivo, [ 18F]FSPG tumor retention was halved seven days after the start of treatment, which preceded radiotherapy-induced tumor shrinkage, thereby confirming [ 18F]FSPG-PET as an early and sensitive marker of radiation response.

Original language	English
Pages (from-to)	28
Journal	npj Imaging
Volume	2
Issue number	1
DOIs	https://doi.org/10.1038/s44303-024-00038-y
Publication status	Published - 9 Aug 2024

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Cite this

@article{04d3b18067fb419f8264388bde9908f7,

title = "[18F]FSPG-PET provides an early marker of radiotherapy response in head and neck squamous cell cancer",

abstract = "The ability to image early treatment response to radiotherapy in head and neck squamous cell carcinoma (HNSCC) will enable the identification of radioresistant tumor volumes suitable for treatment intensification. Here, we propose the system x c - radiotracer (4 S)-4-(3-[ 18F]fluoropropyl)-L-glutamate ([ 18F]FSPG) as a non-invasive method to monitor radiation response in HNSCC. We assessed temporal changes in cell death, antioxidant status, and [ 18F]FSPG retention following a single dose of 10 Gy irradiation in FaDU HNSCC cells. Next, using a fractionated course of radiotherapy, we assessed tumor volume changes and performed [ 18F]FSPG-PET imaging in FaDU-bearing mouse xenografts, followed by ex vivo response assessment. In cells, 10 Gy irradiation reduced [ 18F]FSPG retention, coinciding with the induction of apoptosis and the production of reactive oxygen species. In vivo, [ 18F]FSPG tumor retention was halved seven days after the start of treatment, which preceded radiotherapy-induced tumor shrinkage, thereby confirming [ 18F]FSPG-PET as an early and sensitive marker of radiation response. ",

author = "Khrishanthne Sambasivan and Tyrrell, {Will E} and Rizwan Farooq and Jenasee Mynerich and Edwards, {Richard S} and Muhammet Tanc and Urbano, {Teresa Guerrero} and Witney, {Timothy H}",

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AU - Sambasivan, Khrishanthne

AU - Tyrrell, Will E

AU - Farooq, Rizwan

AU - Mynerich, Jenasee

AU - Edwards, Richard S

AU - Tanc, Muhammet

AU - Urbano, Teresa Guerrero

AU - Witney, Timothy H

PY - 2024/8/9

Y1 - 2024/8/9

N2 - The ability to image early treatment response to radiotherapy in head and neck squamous cell carcinoma (HNSCC) will enable the identification of radioresistant tumor volumes suitable for treatment intensification. Here, we propose the system x c - radiotracer (4 S)-4-(3-[ 18F]fluoropropyl)-L-glutamate ([ 18F]FSPG) as a non-invasive method to monitor radiation response in HNSCC. We assessed temporal changes in cell death, antioxidant status, and [ 18F]FSPG retention following a single dose of 10 Gy irradiation in FaDU HNSCC cells. Next, using a fractionated course of radiotherapy, we assessed tumor volume changes and performed [ 18F]FSPG-PET imaging in FaDU-bearing mouse xenografts, followed by ex vivo response assessment. In cells, 10 Gy irradiation reduced [ 18F]FSPG retention, coinciding with the induction of apoptosis and the production of reactive oxygen species. In vivo, [ 18F]FSPG tumor retention was halved seven days after the start of treatment, which preceded radiotherapy-induced tumor shrinkage, thereby confirming [ 18F]FSPG-PET as an early and sensitive marker of radiation response.

AB - The ability to image early treatment response to radiotherapy in head and neck squamous cell carcinoma (HNSCC) will enable the identification of radioresistant tumor volumes suitable for treatment intensification. Here, we propose the system x c - radiotracer (4 S)-4-(3-[ 18F]fluoropropyl)-L-glutamate ([ 18F]FSPG) as a non-invasive method to monitor radiation response in HNSCC. We assessed temporal changes in cell death, antioxidant status, and [ 18F]FSPG retention following a single dose of 10 Gy irradiation in FaDU HNSCC cells. Next, using a fractionated course of radiotherapy, we assessed tumor volume changes and performed [ 18F]FSPG-PET imaging in FaDU-bearing mouse xenografts, followed by ex vivo response assessment. In cells, 10 Gy irradiation reduced [ 18F]FSPG retention, coinciding with the induction of apoptosis and the production of reactive oxygen species. In vivo, [ 18F]FSPG tumor retention was halved seven days after the start of treatment, which preceded radiotherapy-induced tumor shrinkage, thereby confirming [ 18F]FSPG-PET as an early and sensitive marker of radiation response.

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