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J Nucl Med. 2018 Jul;59(7):1099-1103. doi: 10.2967/jnumed.117.206045. Epub 2018 Mar 1.

Impact of Novel Antidepressants on Cardiac 123I-Metaiodobenzylguanidine Uptake: Experimental Studies on SK-N-SH Cells and Healthy Rabbits.

Author information

1
Division of Nuclear Medicine and Molecular Imaging, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland.
2
Department of Nuclear Medicine, University of Wuerzburg, Wuerzburg, Germany.
3
Comprehensive Heart Failure Center, University of Wuerzburg, Wuerzburg, Germany.
4
Department of Psychiatry, Psychosomatics, and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
5
Department of Nuclear Medicine, Kanazawa University, Kanazawa, Japan; and.
6
Department of Nuclear Medicine, University of Wuerzburg, Wuerzburg, Germany thiguchi@me.com.
7
Department of Biomedical Imaging, National Cardiovascular and Cerebral Center, Suita, Japan.

Abstract

123I-metaiodobenzylguanidine (123I-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 123I-MIBG imaging results. Methods: The inhibition effect of desipramine, escitalopram, venlafaxine, and bupropion on 131I-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 123I-MIBG cardiac uptake, in vivo planar 123I-MIBG scanning of healthy New Zealand White rabbits was performed. Results: The half-maximal inhibitory concentrations of desipramine, escitalopram, venlafaxine, and bupropion on 131I-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 131I-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 123I-MIBG uptake. Conclusion: 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 123I-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 123I-MIBG imaging, in particular, if the patient's neuropsychiatric status would not tolerate withdrawal of a potentially norepinephrine-interfering antidepressant.

KEYWORDS:

123I-MIBG; antidepressant; cardiac sympathetic nerve system; depression; major depressive disorder; myocardial sympathetic innervation imaging

PMID:
29496989
DOI:
10.2967/jnumed.117.206045
[Indexed for MEDLINE]
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