Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

Aim: (‐)‐[F‐18] Norchloro‐fluoro‐homoepibatidine ((‐)‐NCFHEB) is a new and promising tracer for neuroimaging of alpha4beta2 nicotinic acetylcholine receptors with PET. To assess the radiation risk to humans caused by systemic application of the tracer, CD1 mice were injected with (‐)‐NCFHEB. The biodistribution of the tracer and, thereby, resulting organ doses (OD) and the effective dose (ED) were calculated.
Methods: 27 female CD1 mice (weight: 28.2 ± 2.1g) were injected i.v. with 0.75± 0.334MBq of (‐)‐[F18]NCFHEB (specific activity >100GBq/μmol) through the V. caudata lateralis. At 5, 15, 30, 45, 60, 90, 120, 180 and 240 min. p.i. the animals were sacrificed (n=3 per time). The organs (brain, heart, lung, stomach, small intestine, large intestine, liver, kidneys, urinary bladder, spleen, thymus, pancreas, adrenals, ovaries, blood, skin, muscle, skeleton) were isolated, weighed and counted in a γ‐counter to determine mass and radioactivity. The masses of the skeleton and the muscle were extrapolated from tissue samples [1]. Time and mass scales were adapted to the respective human scales [2]. The fractions of activity in source organs were displayed as %ID/g, and %ID/organ for both scales. Time‐activity curves were derived by trapezoidal and exponential fits. The numbers of disintegrations in the source organs were calculated and ODs and the ED was calculatedusing OLINDA.
Results: The urinary bladder receives the highest OD of 104.0 μSv/MBq, followed by the kidneys (24.2 μSv/MBq), uterus (14.1 μSv/MBq), liver (14.0 μSv/MBq), pancreas (14.0 μSv/MBq) and small intestine (14.0 μSv/MBq) The highest contribution to the ED was by urinary bladder (5.2μSv/MBq) followed by the ovaries (2.1μSv/MBq), lower large intestine (1.5μSv/MBq) and red marrow (1.3 μSv/MBq). According to these data, the ED by i.v. application of (‐)‐[F18]NCFHEB
results in an ED of 14.2 μSv/MBq.
Conclusion: The ED as a measure of the overall radiation risk upon i.v. application of about 370 MBq (‐)‐[F‐18] NCFHEB to humans would be 5.3 mSv. This is well within the range of the application of other [F18]‐labeled compounds to humans. This risk assessment encourages to transfer (‐)‐[F‐18]NCFHEB from preclinical to clinical study phases and to further develop as a clinical tool for PET brain imaging.
References: [1] Lindstedt SL, Schaeffer PJ.: Use of allometry in predicting anatomical and physiological parameters of mammals Laboratory Animals (2002) 36, 1‐19 [2] Stabin MJ: Fundamentals of Nuclear Medicine Dosimetry, Springer 2008, ISBN 978‐0‐387‐74578‐7, 237P The trial is granted by the German Federal Ministry of Education and Research (Nr. 01EZ0820)