Université de Strasbourg, CNRS, IPHC UMR 7178, F-67000, Strasbourg, France.
Institut de Cancérologie Strasbourg Europe (ICANS), UNICANCER, Paul Strauss Comprehensive Cancer Center, Radiobiology Laboratory, 67000, Strasbourg, France.
Mol Imaging Biol. 2021 Oct;23(5):724-732. doi: 10.1007/s11307-021-01602-3. Epub 2021 Apr 13.
The main objective of the present study was to compare the 2-deoxy-2-[F]fluoro-D-glucose ([F]-FDG) and 3'-[F]fluoro-3'-deoxythymidine ([F]-FLT) PET imaging biomarkers for the longitudinal follow-up of small animal proton therapy studies in the context of hepatocellular carcinoma (HCC).
SK-HEP-1 cells were injected into NMRI nude mice to mimic human HCC. The behavior of [F]-FDG and [F]-FLT tumor uptake was evaluated after proton therapy procedures. The proton single-fraction doses were 5, 10, and 20 Gy, with a dose rate of 10 Gy/min. The experimental protocol consisted of 8 groups of 10 mice, each group experiencing a particular dose/radiotracer condition. A reference PET exam was performed on each mouse the day before the irradiation procedure, followed by PET exams every 3 days up to 16 days after irradiation.
[F]-FDG uptake showed a linear dose-dependent increase in the first days after treatment (37%, p < 0.05), while [F]-FLT uptake decreased in a dose-dependent manner (e.g., 21% for 5 Gy compared to 10 Gy, p = 1.1e-2). At the later time point, [F]-FDG normalized activity showed an 85% decrease (p < 0.01) for both 10 and 20 Gy doses and no variation for 5 Gy. Conversely, a significant 61% (p = 0.002) increase was observed for [F]-FLT normalized activity at 5 Gy and no variation for higher doses.
We showed that the use of the [F]-FDG and [F]-FLT radiolabeled molecules can provide useful and complementary information for longitudinal follow-up of small animal proton therapy studies in the context of HCC. [F]-FDG PET imaging enables a treatment monitoring several days/weeks postirradiation. On the other hand, [F]-FLT could represent a good candidate to monitor the treatment few days postirradiation, in the context of hypo-fractioned and close irradiation planning. This opens new perspectives in terms of treatment efficacy verification depending on the irradiation scheme.
本研究的主要目的是比较 2-脱氧-2-[F]氟-D-葡萄糖([F]-FDG)和 3'-[F]氟-3'-脱氧胸苷([F]-FLT) PET 成像生物标志物,用于肝癌(HCC)小动物质子治疗研究的纵向随访。
将 SK-HEP-1 细胞注射到 NMRI 裸鼠中,以模拟人类 HCC。在质子治疗后评估[F]-FDG 和[F]-FLT 肿瘤摄取的行为。质子单次剂量分别为 5、10 和 20 Gy,剂量率为 10 Gy/min。实验方案包括 10 只小鼠的 8 组,每组接受特定的剂量/放射性示踪剂条件。在照射前一天对每只小鼠进行参考 PET 检查,然后在照射后 16 天内每 3 天进行一次 PET 检查。
[F]-FDG 摄取在治疗后最初几天呈线性剂量依赖性增加(37%,p < 0.05),而[F]-FLT 摄取呈剂量依赖性减少(例如,5 Gy 与 10 Gy 相比减少 21%,p = 1.1e-2)。在较晚的时间点,10 和 20 Gy 剂量的[F]-FDG 归一化活性分别下降 85%(p < 0.01),而 5 Gy 则没有变化。相反,5 Gy 时[F]-FLT 归一化活性显著增加 61%(p = 0.002),而高剂量则没有变化。
我们表明,使用[F]-FDG 和[F]-FLT 标记的分子可以为 HCC 中小动物质子治疗研究的纵向随访提供有用且互补的信息。[F]-FDG PET 成像能够在照射后数天/数周进行治疗监测。另一方面,[F]-FLT 可能是一种很好的候选物,可在低分割和近距离照射计划的情况下,在照射后几天内监测治疗情况。这为根据照射方案验证治疗效果提供了新的视角。