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Preparation of 99m Tc-PQQ and preliminary biological evaluation for the NMDA receptor.
Pyrroloquinoline quinone (PQQ), an essential nutrient, antioxidant, redox modulator and nerve growth factor found in a class of enzymes called quinoproteins, was labeled with 99m Tc by using stannous fluoride (SnF2 ) method. Radiolabeling qualification, quality control and characterization of 99m Tc-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 of 99m Tc-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 Na99m TcO4 at pH 6 and 25 °C with a response volume of 1 ± 0.1 mL. 99m Tc-PQQ was stable and anionic. Lipid-water partition coefficient of 99m Tc-PQQ was -1.49 ± 0.16. The pharmacokinetics parameters of 99m Tc-PQQ were t 1/2α = 18.16 min, t 1/2β = 100.45 min, K 12 = 0.013 min-1 , K 21 = 0.017 min-1 , K e = 0.016 min-1 , AUC (area under the curve) = 1040.78 ID% g-1 min and CL (plasma clearance) = 0.096 mL min-1 . The dual-exponential equation was Y = 10.88e-0.038 t + 5.21e-0.0069 t . The biodistribution of 99m Tc-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 the 99m Tc-PQQ radioactivity accumulated predominantly in the hippocampus and cortex, which had a high density of N -methyl-d-aspartate Receptor (NMDAR). The enrichment can be blocked by NMDAR redox modulatory site antagonists-ebselen (EB) and 99m Tc-PQQ is therefore a promising candidate for the molecular imaging of NMDAR. To date, however, there have been no studies characterizing 99m Tc-PQQ.
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