Synthesis and evaluation of new technetium-99m complexes as radiopharmaceuticals for heart imaging
Abstract
This project is about synthesis and evaluation of novel Tc-99m complexes as potential radiotracers for heart imaging. More than 50 compounds were synthesized and evaluated. Biodistribution studies were performed in Sprague-Dawley rats to compare the myocardial uptake and excretion kinetics of Tc-99m radiotracers from noncardiac organs with those of the known Tc-99m radiotracers such as 99mTc-seatamibi and 99mTcN-DBODC5. Planar images were also performed to evaluate the utility of Tc-99m complexes as a myocardial perfusion imaging agent. Metabolism studies were carried out by use of Sprague-Dawley rats to study the metabolic fate of Tc-99m complexes. In this project, it was found that cationic characteristic and ether and crown-ether containing chelators have a significant impact on lipophilicity, solution stability, biodistribution and metabolic stability of Tc-99m complexes. Among the compounds, 99mTcN-MPO showed the best result. The heart uptake of 99m TcN-MPO was between that of 99mTc-sestamibi and 99mTc-DBODC5 over the 2 hour period. However, the heart-liver ratio of 99mTcN-MPO (12.75 ± 3.34) at 30 minutes after injection was more than twice that of 99mTc-DBODC5 (6.01 ± 1.45) and 4 times higher than that of 99mTc-sestamibi (2.90 ± 0.22). There was no significant metabolism in the urine and feces sample at 120 minutes after injection. Planar imaging studies suggest that 99m TcN-MPO might be able to give clinically useful images in 30 minutes after inject. In conclusion, 99mTcN-MPO is promising candidate for more pre-clinical evaluations in various animal models.
Degree
Ph.D.
Advisors
Liu, Purdue University.
Subject Area
Medical imaging
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