ToNIC, Toulouse NeuroImaging Center, Université de Toulouse, Inserm, UPS, France; University Hospital, Radiopharmacy Unit, Toulouse, France.
Inserm, UMR1037 CRCT, F-31000 Toulouse, France; Université Toulouse III-Paul Sabatier, UMR1037 CRCT, F-31000 Toulouse, France; Universidad de Costa Rica, CICANUM-Escuela de Física, San José, Costa Rica.
Nucl Med Biol. 2018 Apr;59:1-8. doi: 10.1016/j.nucmedbio.2017.12.003. Epub 2017 Dec 21.
The aim of this work was to study the biodistribution, metabolism and radiation dosimetry of rats injected with [F]FNM using PET/CT images. This novel radiotracer targeting NMDA receptor has potential for investigation for neurological and psychiatric diseases.
Free fraction and stability in fresh human plasma were determined in vitro. PET/CT was performed on anesthetized rats. Organs were identified and 3D volumes of interest (VOIs) were manually drawn on the CT in the center of each organ. Time activity curves (TACs) were created with these VOIs, enabling the calculation of residence times. To confirm these values, ex vivo measurements of organs were performed. Plasma and urine were also collected to study in vivo metabolism. Data was extrapolated to humans, effective doses were estimated using ICRP-60 and ICRP-89 dosimetric models and absorbed doses were estimated using OLINDA/EXM V1.0 and OLINDA/EXM V2.0 (which use weighting factors from ICRP-103 to do the calculations).
The [F]FNM was stable in human plasma and the diffusible free fraction was 53%. As with memantine, this tracer is poorly metabolized in vivo. Ex vivo distributions validated PET/CT data as well as demonstrating a decrease of radiotracer uptake in the brain due to anesthesia. Total effective dose was around 6.11 μSv/MBq and 4.65 μSv/MBq for female and male human dosimetric models, respectively.
This study shows that the presented compound exhibits stability in plasma and plasma protein binding very similar to memantine. Its dosimetry shows that it is suitable for use in humans due to a low total effective dose compared to other PET radiotracers.
本研究旨在通过 PET/CT 图像研究注射 [F]FNM 的大鼠的生物分布、代谢和辐射剂量。这种新型 NMDA 受体放射性示踪剂可能对神经和精神疾病的研究具有潜在价值。
在体外测定游离分数和新鲜人血浆中的稳定性。对麻醉大鼠进行 PET/CT 检查。在 CT 上于每个器官的中心手动识别器官并绘制三维感兴趣区（VOI）。使用这些 VOI 创建时间活性曲线（TAC），以计算停留时间。为了确认这些值，还进行了器官的离体测量。还收集了血浆和尿液以研究体内代谢。将数据外推至人类，使用 ICRP-60 和 ICRP-89 剂量学模型估算有效剂量，并使用 OLINDA/EXM V1.0 和 OLINDA/EXM V2.0（使用 ICRP-103 的权重因子进行计算）估算吸收剂量。
[F]FNM 在人血浆中稳定，可扩散游离分数为 53%。与美金刚一样，该示踪剂在体内代谢不良。离体分布验证了 PET/CT 数据，并证明由于麻醉导致脑内放射性示踪剂摄取减少。女性和男性人体剂量模型的总有效剂量分别约为 6.11 μSv/MBq 和 4.65 μSv/MBq。
本研究表明，所提出的化合物在血浆中表现出稳定性和与美金刚非常相似的血浆蛋白结合。其剂量学研究表明，与其他 PET 放射性示踪剂相比，由于总有效剂量低，因此适合在人类中使用。
