Division of Nuclear Medicine and Molecular Imaging, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Nuclear Medicine, University of Wuerzburg, Wuerzburg, Germany.
J Nucl Med. 2018 Jul;59(7):1099-1103. doi: 10.2967/jnumed.117.206045. Epub 2018 Mar 1.
I-metaiodobenzylguanidine (I-MIBG) has independent prognostic value for risk stratification among heart failure patients, but the use of concomitant medication should not affect its quantitative information. We evaluated whether the 4 classes of antidepressants currently most prescribed as first-line treatment for major depressive disorder (MDD) have the potential to alter I-MIBG imaging results. The inhibition effect of desipramine, escitalopram, venlafaxine, and bupropion on I-MIBG uptake was assessed by in vitro uptake assays using human neuroblastoma SK-N-SH cells. The half-maximal inhibitory concentration of tracer uptake was determined from dose-response curves. To evaluate the effect of intravenous pretreatment with desipramine (1.5 mg/kg) and escitalopram (2.5 or 15 mg/kg) on I-MIBG cardiac uptake, in vivo planar I-MIBG scanning of healthy New Zealand White rabbits was performed. The half-maximal inhibitory concentrations of desipramine, escitalopram, venlafaxine, and bupropion on I-MIBG cellular uptake were 11.9 nM, 7.5 μM, 4.92 μM, and 12.9 μM, respectively. At the maximum serum concentration (as derived by previous clinical trials), the inhibition rates of I-MIBG uptake were 90.6% for desipramine, 25.5% for venlafaxine, 11.7% for bupropion, and 0.72% for escitalopram. A low inhibition rate for escitalopram in the cell uptake study triggered investigation of an in vivo rabbit model: with a dosage considerably higher than used in clinical practice, the noninhibitory effect of escitalopram was confirmed. Furthermore, pretreatment with desipramine markedly reduced cardiac I-MIBG uptake. In the present in vitro binding assay and in vivo rabbit study, the selective serotonin reuptake inhibitor escitalopram had no major impact on neuronal cardiac I-MIBG uptake within therapeutic dose ranges, whereas other types of first-line antidepressants for MDD treatment led to a significant decrease. These preliminary results warrant further confirmatory clinical trials regarding the reliability of cardiac I-MIBG imaging, in particular, if the patient's neuropsychiatric status would not tolerate withdrawal of a potentially norepinephrine-interfering antidepressant.
碘代苄胍（I-MIBG）对心力衰竭患者的风险分层具有独立的预后价值，但同时使用的药物不应影响其定量信息。我们评估了目前作为治疗重度抑郁症（MDD）的一线治疗药物的 4 类抗抑郁药是否有可能改变 I-MIBG 成像结果。通过使用人神经母细胞瘤 SK-N-SH 细胞进行体外摄取测定，评估了去甲丙咪嗪、依地普仑、文拉法辛和安非他酮对 I-MIBG 摄取的抑制作用。从剂量反应曲线确定示踪剂摄取的半最大抑制浓度。为了评估静脉内预处理去甲丙咪嗪（1.5mg/kg）和依地普仑（2.5 或 15mg/kg）对 I-MIBG 心脏摄取的影响，对健康新西兰白兔进行了体内平面 I-MIBG 扫描。去甲丙咪嗪、依地普仑、文拉法辛和安非他酮对 I-MIBG 细胞摄取的半最大抑制浓度分别为 11.9nM、7.5μM、4.92μM 和 12.9μM。在最大血清浓度（根据以前的临床试验得出）时，I-MIBG 摄取的抑制率为去甲丙咪嗪 90.6%、文拉法辛 25.5%、安非他酮 11.7%和依地普仑 0.72%。依地普仑在细胞摄取研究中的低抑制率促使我们对体内兔模型进行了研究：使用比临床实践中高得多的剂量，证实了依地普仑的非抑制作用。此外，去甲丙咪嗪预处理显着降低了心脏 I-MIBG 摄取。在本体外结合测定和体内兔研究中，选择性 5-羟色胺再摄取抑制剂依地普仑在治疗剂量范围内对神经元心脏 I-MIBG 摄取没有重大影响，而治疗 MDD 的其他类型的一线抗抑郁药则导致显着减少。这些初步结果需要进一步的确认性临床试验来证实心脏 I-MIBG 成像的可靠性，特别是如果患者的神经精神状态不能耐受可能干扰去甲肾上腺素的抗抑郁药的停药。
