Rudolf A Werner1,2,3, Ryohei Kobayashi2,3, Mehrbod Som Javadi1, Zoe Köck2, Hiroshi Wakabayashi2,3, Stefan Unterecker4, Kenichi Nakajima5, Constantin Lapa2, Andreas Menke3,4, Takahiro Higuchi6,3,7. 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.
123I-metaiodobenzylguanidine (123I-MIBG) has independent prognostic value for risk stratification among heart failurepatients, 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 humanneuroblastoma 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; Hiroshi Wakabayashi; Xinyu Chen; Nobuyuki Hayakawa; Constantin Lapa; Steven P Rowe; Mehrbod S Javadi; Simon Robinson; Takahiro Higuchi Journal: Sci Rep Date: 2019-11-19 Impact factor: 4.379
Authors: A M Abdelatty; O A M Badr; S A Mohamed; M S Khattab; Sh M Dessouki; O A A Farid; A A Elolimy; O G Sakr; M A Elhady; G Mehesen; M Bionaz Journal: PLoS One Date: 2020-01-10 Impact factor: 3.240
Authors: Hwan Lee; Aladdin Riad; Paul Martorano; Adam Mansfield; Minu Samanta; Vandana Batra; Robert H Mach; John M Maris; Daniel A Pryma; Mehran Makvandi Journal: J Nucl Med Date: 2019-11-01 Impact factor: 11.082
Authors: Rudolf A Werner; Xinyu Chen; Mitsuru Hirano; Steven P Rowe; Constantin Lapa; Mehrbod S Javadi; Takahiro Higuchi Journal: Clin Transl Imaging Date: 2018-07-03