Date of Award
8-2010
Document Type
Open Access
Degree Name
Master of Science (MS)
Department
Biomedical Engineering
First Advisor
Said Audi
Second Advisor
Anne Clough
Third Advisor
Ming Zhao
Abstract
Myocardial infarction (MI) is a condition in which blood supply to the heart is insufficient. MI is associated with two forms of cell death: apoptosis and necrosis. 99mTc-duramycin (99mTc-D) is a novel radiopharmaceutical that detects cell death by recognizing externalized phosphatidylethanolamine. The objective of this study was to develop a compartmental model for 99mTc-D uptake kinetics in normal and infarct myocardium, and utilize this model to compare the uptake kinetics of 99mTc-D in MI with that of another radiopharmaceutical, 99mTc-C2A-GST.
MI was induced in rats which were then injected (i.v.) with 99mTc-D. Rats were sacrificed at 3, 10, 20, 60, and 180 minutes after injection. Normal and infarct myocardial tissue were weighed and measured for tracer uptake by gamma counting. 99mTc-D blood clearance data was also recorded by drawing blood samples at different time points after injection. Results show that 99mTc-D is sequestered in MI, but not in normal myocardium, that the uptake of 99mTc-D in MI is 48% higher than for 99mTc-C2A-GST, and that the blood clearance rate for 99mTc-D is faster than for 99mTc-C2A-GST.
We evaluated the ability of three compartmental models, with different assumptions regarding 99mTc-D uptake kinetics in MI, to interpret the uptake data of 99mTc-D in normal and infarct myocardium. Model 2, which assumes saturable intracellular probe binding kinetics, and Model 3, which assumes saturable vascular and intracellular probe binding kinetics, provided reasonable fits to 99mTc-D uptake data that were not different. Both models suggested a ~3-fold larger number of available binding sites for 99mTc-D as compared to 99mTc-C2A-GST. This is consistent with the fact that phosphatidylethanolamine (99mTc-D binding target) accounts for ~20% of all phospholipids in mammalian cellular membranes as compared to ~7% for phosphatidylethanolamine and phosphatidylserine (99mTc-C2A-GST binding target) combined. Thus, 99mTc-D and 99mTc-C2A-GST appear to detect a consistent level of cell death in the same MI model. Models 2 and 3 differed in terms of the contribution of the smaller molecular weight of 99mTc-D as compared to 99mTc-C2A-GST to 99mTc-D greater uptake in MI. The results of this study provide a basis for quantitative interpretation of 99mTc-D in vivo uptake in MI.