PT  - JOURNAL ARTICLE
AU  - Bernhard Sattler
AU  - Mathias Kranz
AU  - Alexander Starke
AU  - Stephan Wilke
AU  - Cornelius K. Donat
AU  - Winnie Deuther-Conrad
AU  - Marianne Patt
AU  - Andreas Schildan
AU  - Jörg Patt
AU  - René Smits
AU  - Alexander Hoepping
AU  - Peter Schoenknecht
AU  - Jörg Steinbach
AU  - Peter Brust
AU  - Osama Sabri
TI  - Internal Dose Assessment of (–)-<sup>18</sup>F-Flubatine, Comparing Animal Model Datasets of Mice and Piglets with First-in-Human Results
AID  - 10.2967/jnumed.114.137059
DP  - 2014 Nov 01
TA  - Journal of Nuclear Medicine
PG  - 1885--1892
VI  - 55
IP  - 11
4099  - http://jnm.snmjournals.org/content/55/11/1885.short
4100  - http://jnm.snmjournals.org/content/55/11/1885.full
SO  - J Nucl Med2014 Nov 01; 55
AB  - (−)-18F-flubatine is a promising tracer for neuroimaging of nicotinic acetylcholine receptors (nAChRs), subtype α4β2, using PET. Radiation doses after intravenous administration of the tracer in mice and piglets were assessed to determine the organ doses (ODs) and the effective dose (ED) to humans. The results were compared with subsequent clinical investigations in human volunteers. Methods: Twenty-seven female CD1 mice (weight ± SD, 28.2 ± 2.1 g) received intravenous injection of 0.75 ± 0.33 MBq of (−)-18F-flubatine. Up to 240 min after injection, 3 animals per time point were sacrificed and the organs harvested, weighed, and counted in a γ counter to determine mass and activity, respectively. Furthermore, whole-body PET scans of 5 female piglets (age ± SD, 44 ± 3 d; weight ± SD, 13.7 ± 1.7 kg) and 3 humans (2 men and 1 woman; age ± SD, 59.6 ± 3.9 y; weight ± SD, 74.3 ± 3.1 kg) were obtained up to 236 min (piglets) and 355 min (humans) after injection of 186.6 ± 7.4 and 353.7 ± 10.2 MBq of (−)-18F-flubatine, respectively, using a PET/CT scanner. The CT was used for delineation of the organs. Exponential curves were fitted to the time–activity-data, and time and mass scales were adapted to the human anatomy. The ODs were calculated using OLINDA/EXM (version 1.0); EDs were calculated with the tissue-weighting factors of ICRP103. Results: After the injection of (−)-18F-flubatine, there were no adverse or clinically detectable pharmacologic effects in any of the subjects. The highest activities after injection were found in the kidneys, urinary bladder, and liver. The urinary bladder receives the highest OD in all investigated species, followed by the kidneys and the liver for animals and humans, respectively. On the basis of mouse, piglet, and human kinetic data, the projected human ED of (−)-18F-flubatine was estimated to be 12.5 μSv/MBq in mice, 14.7 ± 0.7 μSv/MBq in piglets, and 23.4 ± 0.4 μSv/MBq in humans. Conclusion: As has been demonstrated for other PET radiotracers, preclinical (i.e., animal-derived) dosimetry underestimates the ED to humans, in the current case of (−)-18F-flubatine by 34%–44%.