Understanding the in vivo uptake kinetics of a phosphatidylethanolamine-binding agent (99m)Tc-Duramycin. Nucl Med Biol 2012 Aug;39(6):821-5
Date
04/27/2012Pubmed ID
22534031Pubmed Central ID
PMC3866915DOI
10.1016/j.nucmedbio.2012.02.004Scopus ID
2-s2.0-84863999521 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
INTRODUCTION: (99m)Tc-Duramycin is a peptide-based molecular probe that binds specifically to phosphatidylethanolamine (PE). The goal was to characterize the kinetics of molecular interactions between (99m)Tc-Duramycin and the target tissue.
METHODS: High level of accessible PE is induced in cardiac tissues by myocardial ischemia (30 min) and reperfusion (120 min) in Sprague-Dawley rats. Target binding and biodistribution of (99m)Tc-duramycin were captured using SPECT/CT. To quantify the binding kinetics, the presence of radioactivity in ischemic versus normal cardiac tissues was measured by gamma counting at 3, 10, 20, 60 and 180 min after injection. A partially inactivated form of (99m)Tc-Duramycin was analyzed in the same fashion. A compartment model was developed to quantify the uptake kinetics of (99m)Tc-Duramycin in normal and ischemic myocardial tissue.
RESULTS: (99m)Tc-duramycin binds avidly to the damaged tissue with a high target-to-background radio. Compartment modeling shows that accessibility of binding sites in myocardial tissue to (99m)Tc-Duramycin is not a limiting factor and the rate constant of target binding in the target tissue is at 2.2 ml/nmol/min/g. The number of available binding sites for (99m)Tc-Duramycin in ischemic myocardium was estimated at 0.14 nmol/g. Covalent modification of D15 resulted in a 9-fold reduction in binding affinity.
CONCLUSION: (99m)Tc-Duramycin accumulates avidly in target tissues in a PE-dependent fashion. Model results reflect an efficient uptake mechanism, consistent with the low molecular weight of the radiopharmaceutical and the relatively high density of available binding sites. These data help better define the imaging utilities of (99m)Tc-Duramycin as a novel PE-binding agent.
Author List
Audi S, Li Z, Capacete J, Liu Y, Fang W, Shu LG, Zhao MAuthor
Said Audi PhD Professor in the Biomedical Engineering department at Marquette UniversityMESH terms used to index this publication - Major topics in bold
AnimalsBacteriocins
Biological Transport
Kinetics
Male
Multimodal Imaging
Myocardial Ischemia
Organotechnetium Compounds
Peptides
Phosphatidylethanolamines
Positron-Emission Tomography
Rats
Rats, Sprague-Dawley
Spatio-Temporal Analysis
Tomography, X-Ray Computed
Whole Body Imaging