Kreimerman Ingrid, Mora-Ramirez Erick, Reyes Laura, Bardiès Manuel, Savio Eduardo, Engler Henry
Uruguayan Centre of Molecular Imaging (CUDIM), Radiopharmacy Department, Montevideo, Uruguay.
Inserm, UMR1037 CRCT, F-31000 Toulouse, France.
Curr Radiopharm. 2019;12(1):40-48. doi: 10.2174/1874471011666180830145304.
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.
SR101 N-(3-[¹⁸F]氟丙基)磺酰胺([¹⁸F]SRF101)是我们小组之前合成的一种磺酰罗丹明101衍生物。荧光染料SR101已被报道为啮齿动物体内新皮质中星形胶质细胞的标志物。
本研究旨在对[¹⁸F]SRF101进行毒理学评估，并基于临床前研究估算人体辐射剂量学。
基于从小鼠模型获得的生物动力学数据进行辐射剂量学研究。进行了单剂量毒性研究。选择的毒理学限值<100μg，并选择了对未标记的SRF101采用100安全系数的异速生长比例缩放。
使用OLINDA/EXM V2.0对男性和女性剂量学模型估算的吸收剂量和有效剂量呈现相同趋势。吸收剂量最高总值出现在肠道的不同节段。使用ICRP-89的组织权重因子，男性和女性剂量学模型的平均有效剂量分别为4.03×10⁻³mSv/MBq和5.08×10⁻³mSv/MBq。毒性研究未发现器官或全身重量、食物消耗、血液学或临床化学参数有变化。此外，在组织病理学检查中未发现病变或异常。
SRF101的毒理学评估证实了该放射性示踪剂用于人体给药的生物安全性。剂量学计算表明，[¹⁸F]SRF101的辐射相关风险与临床应用中使用的其他¹⁸F放射性药物处于同一水平。这些研究结果证实，这种新型放射性示踪剂用于人体PET成像将是安全的。
