TY - JOUR
T1 - Impact of novel antidepressants on cardiac 123 I Metaiodobenzyl guanidine uptake
T2 - Experimental studies on SK-N-SH cells and healthy rabbits
AU - Werner, Rudolf A.
AU - Kobayashi, Ryohei
AU - Javadi, Mehrbod Som
AU - Köck, Zoe
AU - Wakabayashi, Hiroshi
AU - Unterecker, Stefan
AU - Nakajima, Kenichi
AU - Lapa, Constantin
AU - Menke, Andreas
AU - Higuchi, Takahiro
N1 - Funding Information:
This work was supported by the Competence Network of Heart Failure, funded by the Integrated Research and Treatment Center (IFB) of the Federal Ministry of Education and Research (BMBF) and the German Research Council (DFG grant HI 1789/3-3). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 701983. No other potential conflict of interest relevant to this article was reported.
Publisher Copyright:
© 2018 by the Society of Nuclear Medicine and Molecular Imaging.
PY - 2018/7/1
Y1 - 2018/7/1
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.
AB - 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.
KW - Antidepressant
KW - Cardiac sympathetic nerve system
KW - Depression
KW - I-MIBG
KW - Major depressive disorder
KW - Myocardial sympathetic innervation imaging
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U2 - 10.2967/jnumed.117.206045
DO - 10.2967/jnumed.117.206045
M3 - Article
C2 - 29496989
AN - SCOPUS:85049411833
SN - 0161-5505
VL - 59
SP - 1099
EP - 1103
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 7
ER -