Department of Medical Biophysics, Western University , London, Ontario , Canada.
Department of Physics and Radiation Oncology, London Regional Cancer Program, London, Ontario , Canada.
Am J Physiol Heart Circ Physiol. 2019 Mar 1;316(3):H586-H595. doi: 10.1152/ajpheart.00273.2018. Epub 2018 Dec 21.
Radiotherapy for the treatment of left-sided breast cancer increases the long-term risk of cardiovascular disease. The purpose of the present study was to noninvasively image the progression of radiation-induced cardiac inflammation in a large animal model using a hybrid PET and MRI system. Five canines were imaged using [F]fluorodeoxyglucose PET to assess changes in myocardial inflammation. All animals were imaged at baseline, 1 wk, and 1, 3, 6, and 12 mo after focused cardiac external beam irradiation with image guidance. Radiation was delivered in a single fraction. The linear quadratic model was used to convert a typical multifractionated heart dose to a corrected single-fraction biologically equivalent dose. Immunohistochemistry was performed on excised left ventricular tissue samples from all five irradiated canines and one nonirradiated control canine to confirm the presence of inflammation. The mean doses delivered to the entire heart, left ventricle, left anterior descending artery, and left circumflex artery were 1.7 ± 0.2, 2.7 ± 0.2, 5.5 ± 0.9, and 1.1 ± 0.4 Gy, respectively. FDG standard uptake values remained persistently elevated compared with baseline (1.1 ± 0.03 vs. 2.6 ± 0.19, P < 0.05). The presence of myocardial inflammation was confirmed histologically and correlated with myocardial dose. This study suggests a global inflammatory response that is persistent up to 12 mo postirradiation. Inflammation PET imaging should be considered in future clinical studies to monitor the early changes in cardiac function that may play a role in the ultimate development of radiation-induced cardiac toxicity. NEW & NOTEWORTHY Using advanced cardiac PET imaging, we have shown the spatial and quantitative relationship between radiation dose deposition and temporal changes in inflammation. We have shown that the progression of radiation-induced cardiac inflammation is immediate and does not subside for up to 1 yr after radiation. Results are presented in a large animal model that closely resembles the size and vessel architecture of humans. The proposed imaging protocol can be easily replicated for clinical use.
放射治疗左乳腺癌会增加长期患心血管疾病的风险。本研究的目的是使用正电子发射断层扫描（PET）和磁共振成像（MRI）混合系统，对大型动物模型中放射诱导的心脏炎症的进展进行非侵入性成像。使用[F]氟脱氧葡萄糖（FDG）PET 评估心肌炎症变化，对 5 只犬进行成像。所有动物均在接受聚焦心脏外照射并进行图像引导后 1 周、1、3、6 和 12 个月时进行基线成像。单次照射剂量。使用线性二次模型将典型的多分割心脏剂量转换为校正的单次分割生物等效剂量。对所有 5 只接受照射的犬和 1 只未接受照射的对照犬的左心室组织样本进行免疫组织化学染色，以确认炎症的存在。整个心脏、左心室、左前降支和左旋支动脉分别接受的平均剂量为 1.7 ± 0.2、2.7 ± 0.2、5.5 ± 0.9 和 1.1 ± 0.4 Gy。与基线相比，FDG 标准摄取值持续升高（1.1 ± 0.03 比 2.6 ± 0.19，P < 0.05）。组织学证实存在心肌炎症，且与心肌剂量相关。该研究表明，放射后 12 个月内存在持续性全身炎症反应。炎症 PET 成像应在未来的临床研究中考虑，以监测心脏功能的早期变化，这些变化可能在放射诱导的心脏毒性的最终发展中发挥作用。
本研究的创新之处在于，使用先进的心脏 PET 成像技术，我们展示了辐射剂量沉积与炎症时间变化之间的空间和定量关系。我们已经表明，放射诱导的心脏炎症的进展是即时的，并且在放射后长达 1 年的时间内不会消退。结果在大小和血管结构与人类非常相似的大型动物模型中呈现。所提出的成像方案可轻松复制用于临床应用。
