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Evaluation of 99mTc(CO)5I as a potential lung perfusion agent
Authors:Alexander E. Miroslavov  Nikolay I. Gorshkov  Alexander L. Lumpov  Anatoly N. Yalfimov  Dmitrii N. Suglobov  Beverley L. Ellis  Rattana Braddock  Anne-Marie Smith  Mary C. Prescott  Richard S. Lawson  Harbans L. Sharma
Affiliation:1. Division of Radiochemical Research, Khlopin Radium Institute, 2nd Murinskii pr. 28, 194021, St Petersburg, Russia;2. Nuclear Medicine Department, Central Research Institute of Roentgenology and Radiology, Leningradskaya str. 70/4, 197000, St Petersburg, Russia;3. Department of Nuclear Medicine, Manchester Royal Infirmary, M13 9WL Manchester, UK;4. Imaging Science and Biomedical Engineering, School of Cancer and Imaging Science, Stopford Building, The University of Manchester, Oxford Road, Manchester M13 9PT
Abstract:IntroductionThe use of 99mTc-macroggregated albumin for lung perfusion imaging is well established in nuclear medicine. However, there have been safety concerns over the use of blood-derived products because of potential contamination by infective agents, for example, Variant Creutzfeldt Jakob Disease. Preliminary work has indicated that Tc(CO)5I is primarily taken up in the lungs following intravenous administration. The aim of this study was to evaluate the biodistribution and pharmacokinetics of 99mTc(CO)5I and its potential as a lung perfusion agent.Methods99mTc(CO)5I was synthesized by carbonylation of 99mTcO4? at 160 atm of CO at 170°C in the presence of HI for 40 min. Radiochemical purity was determined by HPLC using 99Tc(CO)5I as a reference. 99mTc(CO)5I was administered by ear-vein injection to three chinchilla rabbits, and dynamic images were acquired using a gamma camera (Siemens E-cam) over 20 min. Imaging studies were also performed with 99mTc-labeled macroaggregated albumin (99mTc-MAA) and 99mTcO4? for comparison. 99mTc(CO)5I was administered intravenously to Sprague–Dawley rats, and tissue distribution studies were obtained at 15 min and 1 h postinjection. Comparative studies were performed using 99mTc-MAA.ResultsRadiochemical purity, assessed by HPLC, was 98%. The retention time was similar to that of 99Tc(CO)5I. The dynamic images showed that 70% of 99mTc(CO)5I appeared promptly in the lungs and remained constant for at least 20 min. In contrast, 99mTcO4? rapidly washed out of the lungs after administration. As expected 99mTc-MAA showed 90% lung accumulation. The percentage of injected dose per gram of organ ±S.D. at 1 h for 99mTc(CO)5I was as follows: blood, 0.22±0.02; lung, 12.8±2.87; liver, 0.8±0.15; heart, 0.15±0.01; kidney, 0.47±0.08. The percentage of injected dose per organ ±S.D. at 1 h was as follows: lung, 22.47±2.31; liver, 10.53±1.8; heart, 0.18±0.01; kidney, 1.2±0.17. Tissue distribution studies with 99mTc-MAA showed 100% lung uptake.Conclusion99mTc(CO)5I was synthesized with a high radiochemical purity and showed a high accumulation in the lungs. Further work on the mechanism and optimization of lung uptake of 99mTc-pentacarbonyl complexes is warranted.
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