Dosimetry and Toxicity Studies of the Novel Sulfonamide Derivative of Sulforhodamine 101([18F]SRF101) at a Preclinical Level.
PET radiotracers
Preclinical evaluation
[18F]SRF101
dosimetry
tissue-weighting factors
toxicity.
Journal
Current radiopharmaceuticals
ISSN: 1874-4729
Titre abrégé: Curr Radiopharm
Pays: United Arab Emirates
ID NLM: 101468718
Informations de publication
Date de publication:
2019
2019
Historique:
received:
29
06
2018
revised:
03
08
2018
accepted:
27
08
2018
pubmed:
4
9
2018
medline:
21
5
2019
entrez:
4
9
2018
Statut:
ppublish
Résumé
The SR101 N-(3-[18F]Fluoropropyl) sulfonamide ([18F]SRF101) is a Sulforhodamine 101 derivative that was previously synthesised by our group. The fluorescent dye SR101 has been reported as a marker of astroglia in the neocortex of rodents in vivo. The aim of this study was to perform a toxicological evaluation of [18F]SRF101 and to estimate human radiation dosimetry based on preclinical studies. Radiation dosimetry studies were conducted based on biokinetic data obtained from a mouse model. A single-dose toxicity study was carried out. The toxicological limit chosen was <100 μg, and allometric scaling with a safety factor of 100 for unlabelled SRF101 was selected. The absorbed and effective dose estimated using OLINDA/EXM V2.0 for male and female dosimetric models presented the same tendency. The highest total absorbed dose values were for different sections of the intestines. The mean effective dose was 4.03 x10-3 mSv/MBq and 5.08 x10-3 mSv/MBq for the male and female dosimetric models, respectively, using tissue-weighting factors from ICRP-89. The toxicity study detected no changes in the organ or whole-body weight, food consumption, haematologic or clinical chemistry parameters. Moreover, lesions or abnormalities were not found during the histopathological examination. The toxicological evaluation of SRF101 verified the biosafety of the radiotracer for human administration. The dosimetry calculations revealed that the radiation-associated risk of [18F]SRF101 would be of the same order as other 18F radiopharmaceuticals used in clinical applications. These study findings confirm that the novel radiotracer would be safe for use in human PET imaging.
Sections du résumé
BACKGROUND
BACKGROUND
The SR101 N-(3-[18F]Fluoropropyl) sulfonamide ([18F]SRF101) is a Sulforhodamine 101 derivative that was previously synthesised by our group. The fluorescent dye SR101 has been reported as a marker of astroglia in the neocortex of rodents in vivo.
OBJECTIVE
OBJECTIVE
The aim of this study was to perform a toxicological evaluation of [18F]SRF101 and to estimate human radiation dosimetry based on preclinical studies.
METHODS
METHODS
Radiation dosimetry studies were conducted based on biokinetic data obtained from a mouse model. A single-dose toxicity study was carried out. The toxicological limit chosen was <100 μg, and allometric scaling with a safety factor of 100 for unlabelled SRF101 was selected.
RESULTS
RESULTS
The absorbed and effective dose estimated using OLINDA/EXM V2.0 for male and female dosimetric models presented the same tendency. The highest total absorbed dose values were for different sections of the intestines. The mean effective dose was 4.03 x10-3 mSv/MBq and 5.08 x10-3 mSv/MBq for the male and female dosimetric models, respectively, using tissue-weighting factors from ICRP-89. The toxicity study detected no changes in the organ or whole-body weight, food consumption, haematologic or clinical chemistry parameters. Moreover, lesions or abnormalities were not found during the histopathological examination.
CONCLUSION
CONCLUSIONS
The toxicological evaluation of SRF101 verified the biosafety of the radiotracer for human administration. The dosimetry calculations revealed that the radiation-associated risk of [18F]SRF101 would be of the same order as other 18F radiopharmaceuticals used in clinical applications. These study findings confirm that the novel radiotracer would be safe for use in human PET imaging.
Identifiants
pubmed: 30173658
pii: CRP-EPUB-92710
doi: 10.2174/1874471011666180830145304
doi:
Substances chimiques
Radiopharmaceuticals
0
Rhodamines
0
Sulfonamides
0
Fluorodeoxyglucose F18
0Z5B2CJX4D
sulforhodamine 101
FX0ES3271V
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
40-48Informations de copyright
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