Radiopharmaceuticals for Diagnostics of Lung Diseases
Technetium-99m Pentacarbonylhalides as New Lung Imaging Agents
Tech Area / Field
3 Approved without Funding
Khlopin Radium Institute, Russia, St Petersburg
- Ministry of Health / Central Research Institute of Roentgenology and Radiology, Russia, St Petersburg
- Central Manchester and Manchester Children's University Hospitals, UK, Manchester\nBerlin Charite University / ChariteCentrum für Diagnostische und Interventionelle Radiologie und Nuklearmedizin, Germany, Berlin\nNuclear Medicine Clinic Nürnberg, Germany, Nürnberg
Project summaryLungs are a vitally important human organ. There are two ways to diagnose lung diseases using radiopharmaceuticals (RPs): by intravenous injection of an RP (lung perfusion) or by inhalation of a radioactive gas (lung ventilation). Comparison of the results obtained furnishes reliable information on the lung function and structure. The most widely used RPs for studying lung perfusion are macroaggregates and microspheres of albumin labeled with technetium-99m. However, these medications have certain drawbacks. Significant adsorption of the RP on syringe walls and on the injection site does not allow quantitative evaluation of the RP distribution. Today there are no noncolloidal technetium radiopharmaceuticals for diagnostics of lung perfusion. There are some indications that classical technetium radiopharmaceuticals (MIBI) used for studying other organs can also be used for diagnostics of lung diseases. However, the uptake percentage of such RPs in the lung tissue is low, and the quality of the images obtained with them is poor because of the radiation background from other organs (primarily liver).
The lung ventilation is studied using labeled aerosols (e.g., Technegas) and radioactive isotopes of noble gases (Xe, Kr); this procedure requires rather expensive equipment.
Our preliminary studies showed that iodopentacarbonyltechnetium-99m prepared for the first time in our laboratory is selectively taken up by lung tissues. The percentage of 99mTc(CO)5I uptake by lungs, calculated per gram of the tissue, exceeds by more than an order of magnitude the uptake percentage in all the other organs, including liver. The synthesis procedure allows preparation of a pure solution of 99mTc(CO)5I in water, without any impurities. The mechanism of 99mTc(CO)5I uptake by lungs is unknown yet. We also found that pentacarbonyltechnetium halides, being volatile, can be used for studying lung ventilation.
The goal of this project is to work through the procedures for preparing a novel noncolloidal radiopharmaceutical for diagnostics of lung diseases, to study the mechanism of 99mTc(CO)5X uptake by lungs, and to perform preclinical tests of the best representative of 99mTc(CO)5X (X = Cl, Br, I). For the convenience of comparison, studies of lung perfusion and ventilation will be performed with the same compound.
In the course of executing the project, it is intended to examine the affinity of 99mTc(CO)5X for β-adrenoreceptors by blocking them with special agents, and, if there will be no receptor affinity, to assess the perfusion potential of this agent. The affinity of 99mTc(CO)5X for lung tumor cells will also be evaluated.
After elucidating the mechanism of 99mTc(CO)5X uptake by lung tissue and evaluating the affinity of these complexes for lung tumors, it is intended to perform standard preclinical tests of the most promising agent 99mTc(CO)5X (among X = Cl, Br, I). Another goal of the study is to optimize the synthesis of the complexes 99mTc(CO)5X and to evaluate their stability in aqueous solutions.