OBJECTIVE: We investigated the whole-body biodistributions and radiation dosimetry of five (11)C-labeled and one (18)F-labeled radiotracers in human subjects, and compared the results to those obtained from murine biodistribution studies. METHODS: The radiotracers investigated were (11)C-SA4503, (11)C-MPDX, (11)C-TMSX, (11)C-CHIBA-1001, (11)C-4DST, and (18)F-FBPA. Dynamic whole-body positron emission tomography (PET) was performed in three human subjects after a single bolus injection of each radiotracer. Emission scans were collected in two-dimensional mode in five bed positions. Regions of interest were placed over organs identified in reconstructed PET images. The OLINDA program was used to estimate radiation doses from the number of disintegrations of these source organs. These results were compared with the predicted human radiation doses on the basis of biodistribution data obtained from mice by dissection. RESULTS: The ratios of estimated effective doses from the human-derived data to those from the mouse-derived data ranged from 0.86 to 1.88. The critical organs that received the highest absorbed doses in the human- and mouse-derived studies differed for two of the six radiotracers. The differences between the human- and mouse-derived dosimetry involved not only the species differences, including faster systemic circulation of mice and differences in the metabolism, but also measurement methodologies. CONCLUSIONS: Although the mouse-derived effective doses were roughly comparable to the human-derived doses in most cases, considerable differences were found for critical organ dose estimates and pharmacokinetics in certain cases. Whole-body imaging for investigation of radiation dosimetry is desirable for the initial clinical evaluation of new PET probes prior to their application in subsequent clinical investigations.
OBJECTIVE: We investigated the whole-body biodistributions and radiation dosimetry of five (11)C-labeled and one (18)F-labeled radiotracers in human subjects, and compared the results to those obtained from murine biodistribution studies. METHODS: The radiotracers investigated were (11)C-SA4503, (11)C-MPDX, (11)C-TMSX, (11)C-CHIBA-1001, (11)C-4DST, and (18)F-FBPA. Dynamic whole-body positron emission tomography (PET) was performed in three human subjects after a single bolus injection of each radiotracer. Emission scans were collected in two-dimensional mode in five bed positions. Regions of interest were placed over organs identified in reconstructed PET images. The OLINDA program was used to estimate radiation doses from the number of disintegrations of these source organs. These results were compared with the predicted human radiation doses on the basis of biodistribution data obtained from mice by dissection. RESULTS: The ratios of estimated effective doses from the human-derived data to those from the mouse-derived data ranged from 0.86 to 1.88. The critical organs that received the highest absorbed doses in the human- and mouse-derived studies differed for two of the six radiotracers. The differences between the human- and mouse-derived dosimetry involved not only the species differences, including faster systemic circulation of mice and differences in the metabolism, but also measurement methodologies. CONCLUSIONS: Although the mouse-derived effective doses were roughly comparable to the human-derived doses in most cases, considerable differences were found for critical organ dose estimates and pharmacokinetics in certain cases. Whole-body imaging for investigation of radiation dosimetry is desirable for the initial clinical evaluation of new PET probes prior to their application in subsequent clinical investigations.
Authors: Liza Lindenberg; Stephen Adler; Ismail B Turkbey; Francesca Mertan; Anita Ton; Khanh Do; Shivaani Kummar; Esther Mena Gonzalez; Sibaprasad Bhattacharyya; Paula M Jacobs; Peter Choyke Journal: Am J Nucl Med Mol Imaging Date: 2017-09-01
Authors: Eero Rissanen; Jouni Tuisku; Pauliina Luoto; Eveliina Arponen; Jarkko Johansson; Vesa Oikonen; Riitta Parkkola; Laura Airas; Juha O Rinne Journal: J Cereb Blood Flow Metab Date: 2014-11-05 Impact factor: 6.200
Authors: F Bretin; M A Bahri; C Bernard; G Warnock; J Aerts; N Mestdagh; T Buchanan; C Otoul; F Koestler; F Mievis; F Giacomelli; C Degueldre; R Hustinx; A Luxen; A Seret; A Plenevaux; E Salmon Journal: Mol Imaging Biol Date: 2015-08 Impact factor: 3.488
Authors: Gary L Griffiths; Crystal Vasquez; Freddy Escorcia; Jeff Clanton; Liza Lindenberg; Esther Mena; Peter L Choyke Journal: Adv Drug Deliv Rev Date: 2021-12-20 Impact factor: 15.470