Human biodistribution and internal dosimetry of 4-[ 18F]fluorobenzyl-dexetimide: a PET radiopharmaceutical for imaging muscarinic acetylcholine receptors in the brain and heart.

Abstract

4-[18F] fluorobenzyl dexetimide (F-DEX) is the first non-subtype selective fluorine-18 labelled tracer for muscarinic receptors (mAChR) used in humans. A recent first-in-human study found high regional brain uptake with low variation in normal subjects. Disturbance of mAChR has been reported in Alzheimer's and Parkinson's disease, schizophrenia and depression and various cardiac diseases. The following work assesses the biodistribution, organ tracer kinetics and radiation dose associated with F-DEX. Dose calculations were based on activity uptake derived from multiple time point whole body PET CT imaging and the organ-specific dosimetric S-factors derived from the ICRP 133 standard man and woman mathematical phantoms. Effective doses were calculated using the latest ICRP tissue weighting factors. Serial images and time activity curves demonstrate high brain and left ventricular myocardial uptake (5% and 0.65% of injected activity, respectively) with greater retention in brain than myocardium. The mean effective dose was in concordance with other 18F labelled tracers at 19.70 ± 2.27 μSv/MBq. The largest absorbed doses were in the liver (52.91 ± 1.46 μGy/MBq) and heart wall (43.94 ± 12.88 μGy/MBq) for standard man and the liver (61.66 ± 13.61 μGy/MBq) and lungs (40.93 ± 3.11 μGy/MBq) for standard woman. The absorbed dose to all organs, most notably, the red bone marrow (20.03 ± 2.89 μGy/MBq) was sufficiently low to ensure no toxicity after numerous follow-up procedures. The radiation dose associated with an administration of F-DEX is comparable to that of other 18F labelled tracers such as FDG (19.0 μSv/MBq) and lower than tracers used for SPECT imaging of muscarinic receptors (I-DEX 28.5 μSv/MBq). Clinical use would likely result in an effective dose less than 4 mSv for the ICRP 133 standard phantoms after dose optimisation allowing justification for numerous follow-up procedures. Recent results from first in-human studies and a comparatively low radiation dose make F-DEX an attractive option for future applications of imaging muscarinic receptors in the brain. Further investigation of the potential of F-DEX for imaging parasympathetic innervation of the heart may be warranted.