Sambasivan Khrishanthne, Tyrrell Will E, Farooq Rizwan, Mynerich Jenasee, Edwards Richard S, Tanc Muhammet, Urbano Teresa Guerrero, Witney Timothy H
School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.
Department of Clinical Oncology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Npj Imaging. 2024;2(1):28. doi: 10.1038/s44303-024-00038-y. Epub 2024 Aug 9.
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 radiotracer (4)-4-(3-[F]fluoropropyl)-L-glutamate ([F]FSPG) as a non-invasive method to monitor radiation response in HNSCC. We assessed temporal changes in cell death, antioxidant status, and [F]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 [F]FSPG-PET imaging in FaDU-bearing mouse xenografts, followed by ex vivo response assessment. In cells, 10 Gy irradiation reduced [F]FSPG retention, coinciding with the induction of apoptosis and the production of reactive oxygen species. In vivo, [F]FSPG tumor retention was halved seven days after the start of treatment, which preceded radiotherapy-induced tumor shrinkage, thereby confirming [F]FSPG-PET as an early and sensitive marker of radiation response.
对头颈部鳞状细胞癌（HNSCC）早期放疗反应进行成像的能力，将有助于识别适合强化治疗的放射抗拒肿瘤体积。在此，我们提出使用放射性示踪剂（4）-4-（3-[F]氟丙基）-L-谷氨酸（[F]FSPG）的系统，作为一种监测HNSCC放射反应的非侵入性方法。我们评估了FaDU HNSCC细胞单次接受10 Gy照射后细胞死亡、抗氧化状态和[F]FSPG摄取的时间变化。接下来，我们采用分次放疗方案，评估了荷FaDU小鼠异种移植瘤的肿瘤体积变化，并进行了[F]FSPG-PET成像，随后进行了离体反应评估。在细胞中，10 Gy照射降低了[F]FSPG摄取，这与细胞凋亡的诱导和活性氧的产生相一致。在体内，治疗开始后7天，[F]FSPG在肿瘤中的摄取减半，这早于放疗引起的肿瘤缩小，从而证实[F]FSPG-PET是放射反应的早期敏感标志物。
