The present translational study aimed to verify whether serial ¹⁸F-FDG PET/CT predicts doxorubicin cardiotoxicity. Methods: Fifteen athymic mice were treated intravenously with saline (n = 5) or with 5 or 7.5 mg of doxorubicin per kilogram (n = 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 ¹⁸F-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. Results: In mice, LV MRGlu was 17.9 ± 4.4 nmol × min⁻¹ × g⁻¹ at baseline. Doxorubicin selectively and dose-dependently increased this value in the standard-dose (27.9 ± 9 nmol × min⁻¹ × g⁻¹, P < 0.05 vs. controls) and high-dose subgroups (37.2 ± 7.8 nmol × min⁻¹ × g⁻¹, P < 0.01 vs. controls, P < 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, P < 0.01). Multivariate analysis confirmed the predictive value of baseline LV SUV for subsequent cardiac abnormalities. Conclusion: Doxorubicin dose-dependently increases LV MRGlu, particularly in the presence of low baseline ¹⁸F-FDG uptake. These results imply that low myocardial ¹⁸F-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.

目前的转化研究旨在验证系列¹⁸ F-FDG PET / CT是否能预测阿霉素的心脏毒性。方法：将15只无胸腺小鼠静脉注射生理盐水（n = 5）或每公斤阿霉素5或7.5 mg（每只n = 5），并在前后进行动态小动物PET评估左心室（LV）代谢率葡萄糖（MRGlu）。此后，我们回顾性鉴定了69例成功接受了阿霉素，博来霉素，长春碱和达卡巴嗪治疗霍奇金病（HD）的患者，并连续接受了4次治疗¹⁸F-FDG PET / CT扫描。在LV心肌上绘制感兴趣的体积以量化平均SUV。随后所有患者均接受电话采访（中位随访时间为30 mo）；他们中的36人同意接受心电图和经胸超声心动图检查。结果：在小鼠中，LV MRGlu在基线时为17.9±4.4 nmol×min ^-1 ×g ^-1。在标准剂量（27.9±9 nmol×min ^-1 ×g ^-1，与对照组相比，P <0.05）和高剂量亚组（37.2±7.8 nmol×min ^-1 ×克^-1，P <0.01，相对于对照，P与标准剂量相比<0.05）。在HD患者中，阿霉素治疗期间LV SUV逐渐升高，并在随访中持续升高。36例患者中有11例出现了新发的心脏异常（31％）。在这些受试者中，其余患者的治疗前LV SUV明显较低（分别为1.53±0.9对3.34±2.54，P <0.01）。多变量分析证实了基线LV SUV对于随后心脏异常的预测价值。结论：阿霉素剂量依赖性地增加LV MRGlu，特别是在基线¹⁸ F-FDG摄取较低的情况下。这些结果表明低心肌¹⁸HD患者在开始阿霉素化疗之前摄取F-FDG可能预示了化疗诱发的心脏毒性的发生，这表明有必要进行前瞻性临床试验以验证这一假设。