合成并体内评价 p-18F-氟 hippurate 作为一种新的放射性药物，用于通过 PET 评估肾功能。
Synthesis and in vivo evaluation of p-18F-Fluorohippurate as a new radiopharmaceutical for assessment of renal function by PET.
机构信息
Department of Pharmaceutical Sciences, The University of Oklahoma College of Pharmacy, Oklahoma City, Oklahoma 73117, USA.
出版信息
J Nucl Med. 2011 Jan;52(1):147-53. doi: 10.2967/jnumed.110.075895. Epub 2010 Dec 13.
UNLABELLED
The molecular structure of p-18F-fluorohippurate (18F-PFH) is similar to that of p-aminohippurate, a gold standard for the measurement of effective renal plasma flow. The objective of this study was to investigate 18F-PFH as a new PET renal agent.
METHODS
18F-PFH was synthesized by reacting N-succinimidyl-4-18F-fluorobenzoate (18F-SFB) with glycine at 90°C (pH 8) for 20 min. In vitro stability was determined by incubating 18F-PFH in fresh human plasma at 37°C for 60 min. In vivo stability was determined by high-performance liquid chromatography analysis of urine collected from a normal rat at 40 min after injection of 18F-PFH. The plasma protein binding and erythrocyte uptake were determined using plasma collected from a normal rat at 5 min after injection of 18F-PFH. The plasma clearance of 18F-PFH was determined using a single-injection clearance method in normal and probenecid-treated rats. Biodistribution studies were conducted in normal rats at 10 min and 1 h after injection of 18F-PFH. Dynamic PET/CT studies were conducted in normal rats injected with 18F-PFH.
RESULTS
In normal rats, the plasma clearance of 18F-PFH was 4.11±1.09 mL/min/100 g, which reduced by approximately 50% (P=0.03) to 2.01±0.08 mL/min/100 g in probenecid-treated rats. About 45.3% of 18F-PFH was found to associate with plasma proteins in vivo in normal rats. Biodistribution studies of 18F-PFH in normal rats showed 72.1±6.4 percentage injected dose and 88.6±6.2 percentage injected dose, respectively, in urine at 10 min and 1 h after injection. The uptake in other organs was negligible. High-performance liquid chromatography analysis of urine collected from a rat at 40 min after injection of 18F-PFH indicated that it was excreted intact, with no metabolic products. Dynamic PET revealed a rapid clearance of 18F-PFH through the renal-urinary pathway. The PET-derived renograms revealed a time to peak activity of 3.0±1.0 min.
CONCLUSION
These combined results warrant further investigation of 18F-PFH as a radiopharmaceutical for the assessment of renal function by PET.
目的
研究 18F-PFH 作为一种新的 PET 肾显像剂的应用价值。
方法
采用 N-琥珀酰亚胺基-4-18F-氟代苯甲酸（18F-SFB）与甘氨酸在 90°C（pH8）下反应 20min 合成 18F-PFH。通过将 18F-PFH 在新鲜人血浆中于 37°C孵育 60min 来确定其体外稳定性。通过对注射 18F-PFH 后的正常大鼠在 40min 时收集的尿液进行高效液相色谱分析来确定其体内稳定性。通过在注射 18F-PFH 后 5min 从正常大鼠采集的血浆来确定 18F-PFH 的血浆蛋白结合率和红细胞摄取率。采用单次注射清除法在正常和丙磺舒处理的大鼠中测定 18F-PFH 的血浆清除率。在注射 18F-PFH 后 10min 和 1h 时，在正常大鼠中进行 18F-PFH 的生物分布研究。对注射 18F-PFH 的正常大鼠进行动态 PET/CT 研究。
结果
在正常大鼠中，18F-PFH 的血浆清除率为 4.11±1.09mL/min/100g，而在丙磺舒处理的大鼠中，其清除率约降低 50%（P=0.03）至 2.01±0.08mL/min/100g。在正常大鼠中，18F-PFH 约有 45.3%与血浆蛋白结合。在正常大鼠中，18F-PFH 的生物分布研究显示，在注射后 10min 和 1h，尿液中分别有 72.1±6.4%注射剂量和 88.6±6.2%注射剂量，而其他器官的摄取量可以忽略不计。对注射 18F-PFH 后 40min 时从大鼠收集的尿液进行高效液相色谱分析表明，18F-PFH 以完整的形式排泄，没有代谢产物。动态 PET 显示 18F-PFH 通过肾脏-尿途径快速清除。PET 衍生的肾图显示，达峰时间为 3.0±1.0min。
结论
这些综合结果表明，18F-PFH 有必要进一步作为一种放射性药物，通过 PET 评估肾功能。
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