Department of Hematology, Rigshospitalet, University of Copenhagen, section 9322, Blegdamsvej 9, 2100, Copenhagen, Denmark.
Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.
J Nucl Cardiol. 2020 Jun;27(3):931-939. doi: 10.1007/s12350-018-01566-y. Epub 2018 Dec 19.
Doxorubicin is the mainstay of curative lymphoma treatment but is associated with a dose-dependent cardiotoxicity that is often recognized too late to avoid substantial irreversible cardiac injury. Iodine-123 metaiodobenzylguanidine (I-MIBG) is a gamma-emitting tracer that mimics noradrenaline uptake, storage, and release mechanisms in adrenergic presynaptic neurons. I-MIBG scintigraphy can be used for assessment of doxorubicin-induced injury to myocardial adrenergic neurons during treatment and could be the tool for early detection of doxorubicin cardiotoxicity, which is currently lacking.
A total of 37 lymphoma patients scheduled for doxorubicin treatment were included in our study. I-MIBG imaging was performed prior to chemotherapy and after a median of 4 cycles of doxorubicin. Early and late heart-to-mediastinum ratios (H/M and H/M) and washout rate (WOR) were used for evaluation of cardiotoxicity. The prognostic value of I-MIBG results was assessed using left ventricular ejection fraction (LVEF) as measured by cardiac magnetic resonance at 1-year follow-up. We found a post-therapy increase in WOR (including nine patients with > 10% increase), which was not statistically significant (18.6 vs 23.4%, P = 0.09). The difference appeared to be driven by an increase in H/M. LVEF decreased from baseline to 1-year follow-up (64 vs 58%, P = 0.03). LVEF change was not associated with changes in WOR (P = 0.5).
The present study does not provide evidence for I-MIBG imaging as a clinically applicable tool for early detection of doxorubicin-induced cardiotoxicity.
多柔比星是治疗淋巴瘤的主要药物，但与剂量相关的心脏毒性有关，这种毒性通常发现得太晚，无法避免心脏的实质性不可逆损伤。碘-123 间碘苄胍（I-MIBG）是一种发射伽马射线的示踪剂，可模拟去甲肾上腺素在肾上腺素能突触前神经元中的摄取、储存和释放机制。I-MIBG 闪烁显像可用于评估治疗过程中多柔比星对心肌肾上腺素能神经元的损伤，并且可能是早期检测多柔比星心脏毒性的工具，而目前这种工具尚缺乏。
本研究共纳入 37 例计划接受多柔比星治疗的淋巴瘤患者。在化疗前和多柔比星治疗 4 个周期后进行 I-MIBG 显像。使用早期和晚期心脏与纵隔比值（H/M 和 H/M）和洗脱率（WOR）来评估心脏毒性。通过 1 年随访时的心脏磁共振测量左心室射血分数（LVEF）评估 I-MIBG 结果的预后价值。我们发现治疗后 WOR 增加（包括 9 例 WOR 增加>10%），但无统计学意义（18.6%比 23.4%，P=0.09）。这种差异似乎是由 H/M 的增加引起的。LVEF 从基线到 1 年随访时下降（64%比 58%，P=0.03）。LVEF 的变化与 WOR 的变化无关（P=0.5）。
本研究并未提供证据表明 I-MIBG 显像可作为早期检测多柔比星心脏毒性的临床应用工具。
