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 - 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
UR - http://www.scopus.com/inward/record.url?scp=85049411833&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049411833&partnerID=8YFLogxK
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 -