Estimation of the radiation dose by the PET tracer (-)-[F-18]-NCFHEB for imaging of cerebral alpha4beta2 nicotinic acetylcholine receptors (nAChRs) using a preclinical animal model

Objectives: (-)-[F 18]-Norchloro-fluoro-homoepibatidine ((-)-NCFHEB) is a new tracer for neuroimaging of alpha4beta2 nAChRs with PET. To preclinically assess the absorbed radiation dose after application of the tracer, biodistribution, organ doses (OD) and effective dose (ED) were determined after injection of CD1 mice with the radioligand.
Methods: 27 female CD1 mice (weight: 28.2±2.1g) were injected i.v. with 0.75±0.33MBq of (-)-NCFHEB into the V. caudata lateralis. At 5, 15, 30, 45, 60, 90, 120, 180 and 240 min. p.i. the mice were sacrificed (n=3 per time). Brain, heart, lung, stomach, small intestine, large intestine, liver, kidneys, urinary bladder, spleen, thymus, pancreas, adrenals, ovaries, blood, skin, muscle and the skeleton were isolated, weighed and counted in a -counter to determine mass and radioactivity. Time and mass scales were adapted to the human scales. Exponential curves were fitted to the time-activity-data (%ID/g, and %ID/organ). ODs and the ED were calculated using OLINDA.
Results: The highest OD was received by the urinary bladder (104.0 µSv/MBq) and the kidneys (24.2 µSv/MBq). The highest contribution to the ED was by the urinary bladder (5.2 µSv/MBq) and the ovaries (2.1 µSv/MBq). The ED following an i.v. injection of (-)-NCFHEB is 14.2 µSv/MBq.
Conclusions: The ED after i.v. application of 370 MBq (-)-NCFHEB to humans was estimated to be 5.3 mSv. This risk assessment encourages the transfer (-)-NCFHEB from preclinical to clinical studies and to further develop the tracer as a clinical tool for PET imaging of nAChRs.
Research Support: The study was supported by the German Federal Ministry of Education and Research (Nr. 01EZ0820)