Long-term sequestration of fluorinated compounds in tissues after fluvoxamine or fluoxetine treatment: a fluorine magnetic resonance spectroscopy study in vivo

Abstract

Fluorine magnetic resonance spectroscopy (19F MRS), spectroscopic imaging (MRSI) and proton anatomical magnetic resonance imaging (1H MRI) were performed on brains and lower extremities of six subjects in vivo concurrently with HPLC of serum to investigate tissue and plasma drug localization and withdrawal kinetics in humans treated with fluvoxamine or fluoxetine. 19F MRS signal was unexpectedly detected in the lower extremities months after complete disappearance of signal from plasma and brain. MRSI suggested that the lower extremity fluvoxamine signal originated mainly from bone marrow. Results suggest long-term sequestration of these drugs or their metabolites mainly in bone marrow and possibly in surrounding tissue and demonstrate the usefulness of MRS to reveal drug-trapping compartments in the body.

19F‐lanthanide complexes with increased sensitivity for 19F‐MRI: Optimization of the MR acquisition

“…Moreover, through the use of magnetic resonance spectroscopy, information on tracer metabolism can be obtained (4). Previous studies in humans have demonstrated in vivo detection of the 19 F signal from anti-cancer agents (5-7) and antidepressants (8,9). Although the MR properties of the 19 F nucleus are very similar to the proton (yielding good theoretical sensitivity for 19 F based approaches), MR is inherently insensitive compared with nuclear medicine techniques and the in vivo applicability is determined by the achievable concentration of the molecule to be detected.…”

Elucidating the Mechanism(s) Underlying Antipsychotic- and Antidepressant-Mediated Fractures

“…We have also quantified concentrations of aripiprazole and olanzapine (AA drugs) and fluoxetine (SSRI) in mouse marrow following oral dosing, albeit at lower concentrations than RIS 48 . A clinical report using Magnetic Resonance Spectrometry (MRS) indicated that SSRI medications fluoxetine and fluvoxamine accumulated in human marrow and were present in marrow for months following treatment, long after drug disappearance from the brain and blood compartments, supporting the notion that drug exposure in marrow may have clinical relevance for bone turnover 44 . Osteoblasts and osteoclasts can synthesize serotonin, express the serotonin transporter (SERT), and recent studies in rodents indicate that serotonin plays an inhibitory role in osteoblast function [45][46][47] .…”

VatuximabTM: Optimizing Therapeutic Strategies for Prostate Cancer Based on Dynamic MR Tumor Oximetry

“…Moreover, any fluorine MRI detection is readily correlated with the exquisite anatomy provided by routine proton MRI. [16,17,63], gemcitabine [65], and capecitabine [73] are anticancer drugs; fluoxetine [162] and dexfenfluramine [72] have neurological activity, sitafloxacin [66] is an antimicrobial, niflumic acid [67] is a nonsteroidal anti-inflammatory, tecastemzole [68] is an experimental antihistamine and perfluorononane has been proposed for GI imaging [69]. (b) Published 19 F NMR reporter molecules: 6-FPOL (6-fluoropyridoxol) is a pH reporter [11], hexafluorobenzene (HFB) is used for oximetry [10], PFONPG is a gene reporter for b-gal [294], and 5FBAPTA measures …”

“…These can be particularly favorable when they incorporate a CF 3 moiety. Several reports investigated fluoxetine (Prozac) with studies ranging from biopsy tissue extracts to preclinical animal models and human volunteers [70,71,162]. The primary goal has been correlation of concentration with efficacy, for example, Henry et al [70] explored the relative brain concentrations of R and S enantiomers versus a racemic mixture of fluoxetine in separate groups of patients.…”