High efficacy of particle beam therapies against tumors under hypoxia and prediction of the early stage treatment effect using 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography

IF 2.5 4区医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Annals of Nuclear Medicine Pub Date : 2023-10-19 DOI:10.1007/s12149-023-01877-2

Akira Makino, Kyo Kume, Tetsuya Mori, Tetsuya Tsujikawa, Tatsuya Asai, Hidehiko Okazawa, Yasushi Kiyono

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Abstract

Objective

Compared with radiation therapy using photon beams, particle therapies, especially those using carbons, show a high relative biological effectiveness and low oxygen enhancement ratio. Using cells cultured under normoxic conditions, our group reported a greater suppressive effect on cell growth by carbon beams than X-rays, and the subsequent therapeutic effect can be predicted by the cell uptake amount of 3'-deoxy-3'-[¹⁸F]fluorothymidine (¹⁸F-FLT) the day after treatment. On the other hand, a hypoxic environment forms locally around solid tumors, influencing the therapeutic effect of radiotherapy. In this study, the influence of tumor hypoxia on particle therapies and the ability to predict the therapeutic effect using ¹⁸F-FLT were evaluated.

Methods

Using a murine colon carcinoma cell line (colon 26) cultured under hypoxic conditions (1.0% O₂ and 5.0% CO₂), the suppressive effect on cell growth by X-ray, proton, and carbon irradiation was evaluated. In addition, the correlation between decreased ¹⁸F-FLT uptake after irradiation and subsequent suppression of cell proliferation was investigated.

Results

Tumor cell growth was suppressed most efficiently by carbon-beam irradiation. ¹⁸F-FLT uptake temporarily increased the day after irradiation, especially in the low-dose irradiation groups, but then decreased from 50 h after irradiation, which is well correlated with the subsequent suppression on tumor cell growth.

Conclusions

Carbon beam treatment shows a strong therapeutic effect against cells under hypoxia. Unlike normoxic tumors, it is desirable to perform ¹⁸F-FLT positron emission tomography 2–3 days after irradiation for early prediction of the treatment effect.

Graphical Abstract

Abstract Image

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粒子束治疗缺氧下肿瘤的高效性和使用3'-脱氧-3'-[18F]氟胸苷正电子发射断层扫描预测早期治疗效果。

目的：与使用光子束的放射治疗相比，粒子治疗，特别是使用碳的粒子治疗，显示出较高的相对生物有效性和较低的氧气增强率。使用在常氧条件下培养的细胞，我们的研究小组报告称，碳束对细胞生长的抑制作用比X射线更大，随后的治疗效果可以通过治疗后第二天细胞摄取3'-脱氧-3'-[18F]氟胸苷（18F-FLT）的量来预测。另一方面，实体瘤周围局部形成缺氧环境，影响放疗的疗效。在本研究中，评估了肿瘤缺氧对粒子治疗的影响以及使用18F-FLT预测治疗效果的能力。方法：使用在低氧条件下（1.0%O2和5.0%CO2）培养的小鼠结肠癌细胞系（结肠癌26），评估X射线、质子和碳辐射对细胞生长的抑制作用。此外，还研究了照射后18F-FLT摄取减少与随后细胞增殖抑制之间的相关性。结果：碳束照射对肿瘤细胞生长的抑制作用最强。18F-FLT摄取在照射后第二天暂时增加，特别是在低剂量照射组，但从照射后50小时开始下降，这与随后对肿瘤细胞生长的抑制密切相关。结论：碳束对缺氧条件下的细胞有很强的治疗作用。与常氧肿瘤不同，希望在照射后2-3天进行18F-FLT正电子发射断层扫描，以早期预测治疗效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Nuclear Medicine 医学-核医学

CiteScore

4.90

自引率

7.70%

发文量

111

审稿时长

4-8 weeks

期刊介绍： Annals of Nuclear Medicine is an official journal of the Japanese Society of Nuclear Medicine. It develops the appropriate application of radioactive substances and stable nuclides in the field of medicine. The journal promotes the exchange of ideas and information and research in nuclear medicine and includes the medical application of radionuclides and related subjects. It presents original articles, short communications, reviews and letters to the editor.