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

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.

• Authors: Rudolf A Werner, Ryohei Kobayashi, Mehrbod Som Javadi, Zoe Köck, Hiroshi Wakabayashi, Stefan Unterecker, Kenichi Nakajima, Constantin Lapa, Andreas Menke, Takahiro Higuchi
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 59 Issue 7 Pg. 1099-1103 (07 2018) ISSN: 1535-5667 [Electronic] United States
• PMID: 29496989 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Chemical References

• Antidepressive Agents
• 3-Iodobenzylguanidine

Topics

• 3-Iodobenzylguanidine (metabolism)
• Animals
• Antidepressive Agents (pharmacology, therapeutic use)
• Artifacts
• Biological Transport (drug effects)
• Cell Line, Tumor
• Depressive Disorder, Major (diagnosis, drug therapy, metabolism)
• Female
• Health
• Heart (diagnostic imaging, drug effects)
• Humans
• Myocardium (metabolism)
• Rabbits