Impact of novel antidepressants on cardiac 123 I Metaiodobenzyl guanidine uptake: Experimental studies on SK-N-SH cells and healthy rabbits

Rudolf A. Werner, Ryohei Kobayashi, Mehrbod Som Javadi, Zoe Köck, Hiroshi Wakabayashi, Stefan Unterecker, Kenichi Nakajima, Constantin Lapa, Andreas Menke, Takahiro Higuchi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)1099-1103
Number of pages5
JournalJournal of Nuclear Medicine
Volume59
Issue number7
DOIs
Publication statusPublished - Jul 1 2018
Externally publishedYes

Fingerprint

Citalopram
Guanidine
Antidepressive Agents
Desipramine
Rabbits
3-Iodobenzylguanidine
Bupropion
Major Depressive Disorder
Clinical Trials
Serotonin Uptake Inhibitors
Neuroblastoma
Norepinephrine
Therapeutics
Heart Failure
Serum
Inhibition (Psychology)
Venlafaxine Hydrochloride

Keywords

  • I-MIBG
  • Antidepressant
  • Cardiac sympathetic nerve system
  • Depression
  • Major depressive disorder
  • Myocardial sympathetic innervation imaging

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Impact of novel antidepressants on cardiac 123 I Metaiodobenzyl guanidine uptake : Experimental studies on SK-N-SH cells and healthy rabbits. / Werner, Rudolf A.; Kobayashi, Ryohei; Javadi, Mehrbod Som; Köck, Zoe; Wakabayashi, Hiroshi; Unterecker, Stefan; Nakajima, Kenichi; Lapa, Constantin; Menke, Andreas; Higuchi, Takahiro.

In: Journal of Nuclear Medicine, Vol. 59, No. 7, 01.07.2018, p. 1099-1103.

Research output: Contribution to journalArticle

Werner, RA, Kobayashi, R, Javadi, MS, Köck, Z, Wakabayashi, H, Unterecker, S, Nakajima, K, Lapa, C, Menke, A & Higuchi, T 2018, 'Impact of novel antidepressants on cardiac 123 I Metaiodobenzyl guanidine uptake: Experimental studies on SK-N-SH cells and healthy rabbits', Journal of Nuclear Medicine, vol. 59, no. 7, pp. 1099-1103. https://doi.org/10.2967/jnumed.117.206045
Werner, Rudolf A. ; Kobayashi, Ryohei ; Javadi, Mehrbod Som ; Köck, Zoe ; Wakabayashi, Hiroshi ; Unterecker, Stefan ; Nakajima, Kenichi ; Lapa, Constantin ; Menke, Andreas ; Higuchi, Takahiro. / Impact of novel antidepressants on cardiac 123 I Metaiodobenzyl guanidine uptake : Experimental studies on SK-N-SH cells and healthy rabbits. In: Journal of Nuclear Medicine. 2018 ; Vol. 59, No. 7. pp. 1099-1103.
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abstract = "123 I-metaiodobenzylguanidine ( 123 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 123 I-MIBG imaging results. Methods: The inhibition effect of desipramine, escitalopram, venlafaxine, and bupropion on 131 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 123 I-MIBG cardiac uptake, in vivo planar 123 I-MIBG scanning of healthy New Zealand White rabbits was performed. Results: The half-maximal inhibitory concentrations of desipramine, escitalopram, venlafaxine, and bupropion on 131 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 131 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 123 I-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 123 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 123 I-MIBG imaging, in particular, if the patient's neuropsychiatric status would not tolerate withdrawal of a potentially norepinephrine-interfering antidepressant.",
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AU - Werner, Rudolf A.

AU - Kobayashi, Ryohei

AU - Javadi, Mehrbod Som

AU - Köck, Zoe

AU - Wakabayashi, Hiroshi

AU - Unterecker, Stefan

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AU - Menke, Andreas

AU - Higuchi, Takahiro

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N2 - 123 I-metaiodobenzylguanidine ( 123 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 123 I-MIBG imaging results. Methods: The inhibition effect of desipramine, escitalopram, venlafaxine, and bupropion on 131 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 123 I-MIBG cardiac uptake, in vivo planar 123 I-MIBG scanning of healthy New Zealand White rabbits was performed. Results: The half-maximal inhibitory concentrations of desipramine, escitalopram, venlafaxine, and bupropion on 131 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 131 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 123 I-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 123 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 123 I-MIBG imaging, in particular, if the patient's neuropsychiatric status would not tolerate withdrawal of a potentially norepinephrine-interfering antidepressant.

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KW - Cardiac sympathetic nerve system

KW - Depression

KW - Major depressive disorder

KW - Myocardial sympathetic innervation imaging

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