Nuclear Medicine, IRCCS-AOU San Martino-IST and University of Genoa, Genoa, Italy.
Nuclear Medicine Unit, Department of Radiology, Tübingen, Germany.
J Nucl Med. 2017 Oct;58(10):1638-1645. doi: 10.2967/jnumed.117.191122. Epub 2017 Jun 23.
The present translational study aimed to verify whether serial F-FDG PET/CT predicts doxorubicin cardiotoxicity. Fifteen athymic mice were treated intravenously with saline ( = 5) or with 5 or 7.5 mg of doxorubicin per kilogram ( = 5 each) and underwent dynamic small-animal PET beforehand and afterward to estimate left ventricular (LV) metabolic rate of glucose (MRGlu). Thereafter, we retrospectively identified 69 patients who had been successfully treated with a regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine for Hodgkin disease (HD) and had undergone 4 consecutive F-FDG PET/CT scans. Volumes of interest were drawn on LV myocardium to quantify mean SUV. All patients were subsequently interviewed by telephone (median follow-up, 30 mo); 36 of them agreed to undergo electrocardiography and transthoracic echocardiography. In mice, LV MRGlu was 17.9 ± 4.4 nmol × min × g at baseline. Doxorubicin selectively and dose-dependently increased this value in the standard-dose (27.9 ± 9 nmol × min × g, < 0.05 vs. controls) and high-dose subgroups (37.2 ± 7.8 nmol × min × g, < 0.01 vs. controls, < 0.05 vs. standard-dose). In HD patients, LV SUV showed a progressive increase during doxorubicin treatment that persisted at follow-up. New-onset cardiac abnormalities appeared in 11 of 36 patients (31%). In these subjects, pretherapy LV SUV was markedly lower with respect to the remaining patients (1.53 ± 0.9 vs. 3.34 ± 2.54, respectively, < 0.01). Multivariate analysis confirmed the predictive value of baseline LV SUV for subsequent cardiac abnormalities. Doxorubicin dose-dependently increases LV MRGlu, particularly in the presence of low baseline F-FDG uptake. These results imply that low myocardial F-FDG uptake before the initiation of doxorubicin chemotherapy in HD patients may predict the development of chemotherapy-induced cardiotoxicity, suggesting that prospective clinical trials are warranted to test this hypothesis.
本转化研究旨在验证连续 F-FDG PET/CT 是否可预测多柔比星心脏毒性。15 只无胸腺小鼠分别经静脉给予生理盐水（ = 5）或 5 或 7.5mg/kg 的多柔比星（每组各 5 只），并在给药前后进行小动物动态 PET 以评估左心室（LV）葡萄糖代谢率（MRGlu）。随后，我们回顾性地确定了 69 例成功接受多柔比星、博来霉素、长春碱和达卡巴嗪方案治疗霍奇金病（HD）的患者，并进行了 4 次连续 F-FDG PET/CT 扫描。在 LV 心肌上勾画感兴趣区以定量平均 SUV。所有患者随后均通过电话进行了访谈（中位随访时间为 30 个月）；其中 36 例同意进行心电图和经胸超声心动图检查。在小鼠中，LV MRGlu 在基线时为 17.9 ± 4.4 nmol×min×g。多柔比星以剂量依赖性的方式选择性地增加了标准剂量组（27.9 ± 9 nmol×min×g， < 0.05 与对照组相比）和高剂量组（37.2 ± 7.8 nmol×min×g， < 0.01 与对照组相比， < 0.05 与标准剂量组相比）中的这一数值。在 HD 患者中，LV SUV 在多柔比星治疗期间呈进行性增加，并在随访时持续存在。36 例患者中有 11 例（31%）出现新发心脏异常。在这些患者中，与其余患者相比，治疗前的 LV SUV 明显降低（分别为 1.53 ± 0.9 与 3.34 ± 2.54， < 0.01）。多变量分析证实了基线 LV SUV 对随后发生心脏异常的预测价值。多柔比星以剂量依赖性方式增加 LV MRGlu，尤其是在基线 F-FDG 摄取较低时。这些结果表明，HD 患者在开始多柔比星化疗前的心肌 F-FDG 摄取较低可能预测化疗诱导性心脏毒性的发生，这表明有必要进行前瞻性临床试验来检验这一假说。
