Authors:Jiankang Zhang, Xingqin Zhou, and Xiaofeng Qin
One novel styrylpyridine derivatives(AV-45) coupled with 99mTc complex was synthesized. 99mTc-BAT-AV-45 was prepared by a ligand exchange reaction employing sodium glucoheptonate, and effects of the amount of ligand,
stannous chloride, sodium glucoheptonate and pH value of reaction mixture on the radiolabeling yield were studied in details.
Quality control was performed by thin layer chromatography and high performance liquid chromatography. Besides the stability,
partition coefficient and electrophoresis of 99mTc-BAT-AV-45 were also investigated. The results showed that the average radiolabeling yield was (95 ± 1%) and 99mTc-BAT-AV-45 with suitable lipophilicity was stable and uncharged at physiological pH.
Pyrroloquinoline quinone (PQQ), an essential nutrient, antioxidant, redox modulator and nerve growth factor found in a class
of enzymes called quinoproteins, was labeled with 99mTc by using stannous fluoride (SnF2) method. Radiolabeling qualification, quality control and characterization of 99mTc-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 99mTc-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 Na99mTcO4 at pH 6 and 25 °C with a response volume of 1 ± 0.1 mL. 99mTc-PQQ was stable and anionic. Lipid–water partition coefficient of 99mTc-PQQ was −1.49 ± 0.16. The pharmacokinetics parameters of 99mTc-PQQ were t1/2α = 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−1 min and CL (plasma clearance) = 0.096 mL min−1. The dual-exponential equation was Y = 10.88e−0.038t + 5.21e−0.0069t. The biodistribution of 99mTc-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 99mTc-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 99mTc-PQQ is therefore a promising candidate for the molecular imaging of NMDAR. To date, however, there have been no studies