Biodistribution and radiation dosimetry of (-)-F18-NCFHEB, a new tracer for imaging of cerebral alpha4beta2 nicotinic acetylcholine receptors (nAChRs) with PET

Objectives: (-)-[F-18]Norchloro-fluoro-homoepibatidine ((-)-NCFHEB) is a new tracer for neuroimaging of alpha4beta2 nAChRs with PET. To assess the putative radiation risk after application of the radioligand, the biodistribution, organ doses (OD) and the effective dose (ED) were determined in a phase 0/1 trial.
Methods: Whole body dosimetry of (-)-NCFHEB was performed in 3 healthy volunteers (59.6±3.9a; weight 74.3±3.1kg; 2m, 1f). The subjects were sequentially PET/CT-imaged up to 7h post i.v. injection of 353.7±10.2 MBq of(-)-NCFHEB on a SIEMENS Biograph16 PET/CT-system with 9 bed positions (BP) per frame, 1.5-6min/BP, CT-attenuation correction (AC) and iterative reconstruction (OSEM, 4 iterations, 8 subsets). All micturated urine was collected up to 7 hours post injection. Urine samples were weighed and measured for radioactivity concentration [Bq/ccm] in a well counter. All relevant organs were defined by volumes of interest using the structural information from the AC-CT. Exponential curves were fitted to the time-activity-data. The ODs were calculated using the adult male model with OLINDA. The ED was calculated using tissue weighing factors as published in the ICRP 103/2007.
Results: The fraction of radioactivity that was eliminated via urine was 22.2±1.2%. The highest OD was received by the urinary bladder (80.2±37.8), followed by the liver (44.7±5.4) and the kidneys (38.6±5.1). The highest contribution to the ED was by the lungs (3.7±0.6), the urinary bladder (3.2±1.5) and the stomach (2.9±0.7). The ED by i.v. application of (-)-NCFHEB is 22.6±0.7 (all in [μSv/MBq]).
Conclusion: The ED after i.v. application of 370 MBq (-)-NCFHEB is 8.3 mSv. This is well in accordance to values obtained with other [F-18]-labeled compounds. These favorable dosimetry data prove the tolerability of the radiation risk caused by the tracer and encourage the further development of (-)-NCFHEB as a clinical tool for imaging of alpha4beta2 nAChRs with PET.
References: The trial is granted by the German Federal Ministry of Education and Research (Nr. 01EZ0820)