Evaluation of 99mTc(CO)5I as a potential lung perfusion agent

Miroslavov, Alexander E.; Gorshkov, Nikolay I.; Lumpov, Alexander L.; Yalfimov, Anatoly N.; Suglobov, Dmitrii N.; Ellis, Beverley L.; Braddock, Rattana; Smith, Anne-Marie; Prescott, Mary C.; Lawson, Richard S.; Sharma, Harbans L.

doi:10.1016/j.nucmedbio.2008.10.017

« Previous Next »Nuclear Medicine and Biology
Volume 36, Issue 1 , Pages 73-79, January 2009

Evaluation of ^99mTc(CO)₅I as a potential lung perfusion agent☆

Alexander E. Miroslavov
- Division of Radiochemical Research, Khlopin Radium Institute, 2nd Murinskii pr. 28, 194021, St Petersburg, Russia
Nikolay I. Gorshkov
- Division of Radiochemical Research, Khlopin Radium Institute, 2nd Murinskii pr. 28, 194021, St Petersburg, Russia
Alexander L. Lumpov
- Division of Radiochemical Research, Khlopin Radium Institute, 2nd Murinskii pr. 28, 194021, St Petersburg, Russia
Anatoly N. Yalfimov
- Nuclear Medicine Department, Central Research Institute of Roentgenology and Radiology, Leningradskaya str. 70/4, 197000, St Petersburg, Russia
Dmitrii N. Suglobov
- Division of Radiochemical Research, Khlopin Radium Institute, 2nd Murinskii pr. 28, 194021, St Petersburg, Russia
Beverley L. Ellis
- Department of Nuclear Medicine, Manchester Royal Infirmary, M13 9WL Manchester, UK
- Corresponding author. Tel.: +441612768759; fax: +441612768023.
Rattana Braddock
- Imaging Science and Biomedical Engineering, School of Cancer and Imaging Science, Stopford Building, The University of Manchester, Oxford Road, Manchester M13 9PT
Anne-Marie Smith
- Imaging Science and Biomedical Engineering, School of Cancer and Imaging Science, Stopford Building, The University of Manchester, Oxford Road, Manchester M13 9PT
Mary C. Prescott
- Department of Nuclear Medicine, Manchester Royal Infirmary, M13 9WL Manchester, UK
Richard S. Lawson
- Department of Nuclear Medicine, Manchester Royal Infirmary, M13 9WL Manchester, UK
Harbans L. Sharma
- Imaging Science and Biomedical Engineering, School of Cancer and Imaging Science, Stopford Building, The University of Manchester, Oxford Road, Manchester M13 9PT

Received 22 April 2008; received in revised form 15 October 2008; accepted 27 October 2008.

Abstract

Introduction

The 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.

Methods

^99mTc(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.

Results

Radiochemical 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.

Conclusion

^99mTc(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.

Keywords: Lung perfusion, Technetium-99m carbonyl