Biodistribution and dosimetry of ¹²³I-mZIENT: a novel ligand for imaging serotonin transporters.
OBJECTIVE
123I-labelled mZIENT (2β-carbomethoxy-3β-(3′-((Z)-2-iodoethenyl)phenyl)nortropane) has been developed as a radioligand for the serotonin transporter. The aim of this preliminary study was to assess its whole-body biodistribution in humans and estimate dosimetry.


METHODS
Three healthy controls and three patients receiving selective serotonin reuptake inhibitor (SSRI) therapy for depression were included (two men, four women, age range 41-56 years). Whole-body imaging, brain SPECT imaging and blood and urine sampling were performed. Whole-body images were analysed using regions of interest (ROIs), time-activity curves were derived using compartmental analysis and dosimetry estimated using OLINDA software. Brain ROI analysis was performed to obtain specific-to-nonspecific binding ratios in the midbrain, thalamus and striatum.


RESULTS
Initial high uptake in the lungs decreased in later images. Lower uptake was seen in the brain, liver and intestines. Excretion was primarily through the urinary system. The effective dose was estimated to be of the order of 0.03 mSv/MBq. The organ receiving the highest absorbed dose was the lower large intestine wall. Uptake in the brain was consistent with the known SERT distribution with higher specific-to-nonspecific binding in the midbrain, thalamus and striatum in healthy controls compared with patients receiving SSRI therapy.


CONCLUSIONS
¹²³I-mZIENT may be a promising radioligand for imaging the serotonin transporters in humans with acceptable dosimetry.
Department of Nuclear Medicine, Southern General Hospital, NHS Greater Glasgow & Clyde, 1345 Govan Rd, Glasgow G51 4TF, UK. alice.nicol@ggc.scot.nhs.uk
Alice
A
Nicol
Rajeev
R
Krishnadas
Sue
S
Champion
Gilles
G
Tamagnan
Jeffrey S
JS
Stehouwer
Mark M
MM
Goodman
Donald M
DM
Hadley
Sally L
SL
Pimlott
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D016022:Case-Control Studies; D003863:Depression / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008024:Ligands; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods*; D009662:Nortropanes / Q000378:metabolism / Q000493:pharmacokinetics*; D011874:Radiometry; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D015899:Tomography, Emission-Computed, Single-Photon
D007457:Iodine Radioisotopes; D008024:Ligands; D009662:Nortropanes; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C472792:2-carbomethoxy-3-(4'-(2-iodoethenyl)phenyl)nortropane