Preparation of (99m)Tc-PQQ and preliminary biological evaluation for the NMDA receptor.
Preparation of (99m)Tc-PQQ and preliminary biological evaluation for the NMDA receptor.
复制标题
99mTc-PQQ的制备及NMDA受体的初步生物学评价
DOI：
10.1007/s10967-010-0845-5
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发表时间：
2011
影响因子：
1.6
通讯作者：
Zhang R
中科院分区：
文献类型：
--
作者：
Kong Y;Zhou X;Cao G;Xu X;Zou M;Qin X;Zhang R
Pyrroloquinoline quinone (PQQ), an essential nutrient, antioxidant, redox modulator and nerve growth factor found in a class of enzymes called quinoproteins, was labeled with99mTc by using stannous fluoride (SnF2) method. Radiolabeling qualification, quality control and characterization of99mTc-PQQ and its biodistribution studies in mice were performed and discussed. Effects of pH values, temperature, time and reducing agents concentration on the radiolabeling yield were investigated. The quality control procedure of99mTc-PQQ was determined by thin layer chromatography (TLC), radio high-performance liquid chromatography (RHPLC) and paper electrophoresis methods. The average radiolabeling yield was 94 ± 1% under optimum conditions of 0.99 mg of PQQ, 30 μg of SnF2, 0.5 mg of ethylenediaminetetraacetic acid disodium salt (EDTA-2Na) and 18.5 MBq of Na99mTcO4at pH 6 and 25 °C with a response volume of 1 ± 0.1 mL.99mTc-PQQ was stable and anionic. Lipid-water partition coefficient of99mTc-PQQ was -1.49 ± 0.16. The pharmacokinetics parameters of99mTc-PQQ weret1/2α= 18.16 min,t1/2β= 100.45 min,K12= 0.013 min-1,K21= 0.017 min-1,Ke= 0.016 min-1, AUC (area under the curve) = 1040.78 ID% g-1min and CL (plasma clearance) = 0.096 mL min-1. The dual-exponential equation wasY= 10.88e-0.038t+ 5.21e-0.0069t. The biodistribution of99mTc-PQQ was studied in ICR (Institute for Cancer Research 7701 Burhelme Are., Fox Chase, Philadelphia, PA 1911 USA) mice. In vitro autoradiographic studies clearly showed that the99mTc-PQQ radioactivity accumulated predominantly in the hippocampus and cortex, which had a high density ofN-methyl-d-aspartate Receptor (NMDAR). The enrichment can be blocked by NMDAR redox modulatory site antagonists-ebselen (EB) and99mTc-PQQ is therefore a promising candidate for the molecular imaging of NMDAR. To date, however, there have been no studies characterizing99mTc-PQQ.
