Effect of Serotonin-Specific Antidepressant on Radiolabeled Metaiodobenzylguanidine (MIBG) Uptake

Objectives Radiolabeled metaiodobenzylguanidine (MIBG) scintigraphy had been widely available not only for risk stratification of heart failure patients, but also for differential diagnosis of dementia with lewy bodies. Depression is one of the most common co-morbidities in such patients. Pharmacological interference on cardiac ¹²³I-MIBG uptake with conventional antidepressants via inhibiting norepinephrine transport is reported, but influence of the recently introduced antidepressant serotonin selective reuptake inhibitor (SSRI) are not yet determined.

Methods In-vitro binding assay in cell membrane overexpressing human NET (hNET membrane, PerkinElmer) was conducted. Aliquots of membrane suspensions were incubated for 120 min at 4 degree with ¹³¹I-MIBG and 100 ng/mL escitalopram (SSRI). Non-specific binding was determined by incubation buffer with 10 ng/mL desipramine (tricyclic antidepressant, TCA) and control buffer with no inhibitors. In healthy New Zealand White rabbits, in-vivo planar 10 min ¹²³I-MIBG scans utilizing a clinical SPECT system (Siemens) were performed 2.5 hours after intravenous ¹²³I-MIBG administration (50MBq per animal) under general isoflurane anesthesia. Imaging was conducted using 3 different pharmacological pretreatments 10 min before tracer administration: 1) desipramine (1.5 mg/kg weight IV), 2) escitalopram (2.5 or 15 mg/kg weight IV) and 3) saline-treated controls. Heart-to-mediastinum ratios (HMR) were calculated by dividing the count mediastinal ROI.

Results In-vitro binding assay confirmed no interference of escitalopram on MIBG binding to the hNIS (Specific binding: escitalopram 100 ng/mL vs. controls = 185.5 ± 67.7 vs. 154.2 ± 60.0, n.s.). Imaging study showed clear focal cardiac ¹²³I-MIBG uptake in all control animals. Desipramine pretreatment led to a marked reduction of the cardiac ¹²³I-MIBG uptake (HMR: 1.94 ± 0.22 vs. 1.23 ± 0.13, p<0.01). On the other hand, there was no significant pharmacological influence of escitalopram, even in blood concentrations being considerably higher than in clinical practice (escitalopram 2.5 mg/kg, HMR: 2.01 ± 0.13, escitalopram 15 mg/kg, HMR: 2.05 ± 0.19, n.s. vs. controls).

Conclusions In the present in vitro binding assay and in-vivo rabbit study, we demonstrated that high dose of serotonin selective antidepressant escitalopram has no major interference on neuronal ¹²³I-MIBG uptake. Results suggested potential clinical use of MIBG imaging under serotonin selective antidepressant treatment and warrant to conduct confirmatory clinical trials.

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