The Feasibility of Imaging Myocardial Ischemic/Reperfusion Injury Using ^99mTc-labeled Duramycin in a Porcine Model

Authors

Lei Wang, Chinese Academy of Medical Science
Feng Wang, Nanjing Medical University
Wei Fang, Chinese Academy of Medical ScienceFollow
Steven E. Johnson, Northwestern University
Said H. Audi, Marquette UniversityFollow
Michael Zimmer, Northwestern Memorial HospitalFollow
Thomas A. Holly, Northwestern University
Daniel C. Lee, Northwestern University
Bao Zhu, Nanjing Medical University
Haibo Zhu, Institute of Materia Medica
Ming Zhao, Northwestern UniversityFollow

Document Type

Article

Language

eng

Format of Original

7 p.

Publication Date

2-2015

Publisher

Elsevier

Source Publication

Nuclear Medicine and Biology

Source ISSN

0969-8051

Original Item ID

doi: 10.1016/j.nucmedbio.2014.09.002

Abstract

When pathologically externalized, phosphatidylethanolamine (PE) is a potential surrogate marker for detecting tissue injuries. ^99mTc-labeled duramycin is a peptide-based imaging agent that binds PE with high affinity and specificity. The goal of the current study was to investigate the clearance kinetics of ^99mTc-labeled duramycin in a large animal model (normal pigs) and to assess its uptake in the heart using a pig model of myocardial ischemia–reperfusion injury.

Methods

The clearance and distribution of intravenously injected ^99mTc-duramycin were characterized in sham-operated animals (n = 5). In a closed chest model of myocardial ischemia, coronary occlusion was induced by balloon angioplasty (n = 9). ^99mTc-duramycin (10–15 mCi) was injected intravenously at 1 hour after reperfusion. SPECT/CT was acquired at 1 and 3 hours after injection. Cardiac tissues were analyzed for changes associated with acute cellular injuries. Autoradiography and gamma counting were used to determine radioactivity uptake. For the remaining animals, ^99mTc-tetrafosamin scan was performed on the second day to identify the infarct site.

Results

Intravenously injected ^99mTc-duramycin cleared from circulation predominantly via the renal/urinary tract with an α-phase half-life of 3.6 ± 0.3 minutes and β-phase half-life of 179.9 ± 64.7 minutes. In control animals, the ratios between normal heart and lung were 1.76 ± 0.21, 1.66 ± 0.22, 1.50 ± 0.20 and 1.75 ± 0.31 at 0.5, 1, 2 and 3 hours post-injection, respectively. The ratios between normal heart and liver were 0.88 ± 0.13, 0.80 ± 0.13, 0.82 ± 0.19 and 0.88 ± 0.14. In vivo visualization of focal radioactivity uptake in the ischemic heart was attainable as early as 30 min post-injection. The in vivo ischemic-to-normal uptake ratios were 3.57 ± 0.74 and 3.69 ± 0.91 at 1 and 3 hours post-injection, respectively. Ischemic-to-lung ratios were 4.89 ± 0.85 and 4.93 ± 0.57; and ischemic-to-liver ratios were 2.05 ± 0.30 to 3.23 ± 0.78. The size of ^99mTc-duramycin positive myocardium was qualitatively larger than the infarct size delineated by the perfusion defect in ^99mTc-tetrafosmin uptake. This was consistent with findings from tissue analysis and autoradiography.

Conclusion

^99mTc-duramycin was demonstrated, in a large animal model, to have suitable clearance and biodistribution profiles for imaging. The agent has an avid target uptake and a fast background clearance. It is appropriate for imaging myocardial injury induced by ischemia/reperfusion.

Comments

Accepted version. Nuclear Medicine and Biology, Vol. 42, No. 2 (February 2015): 198-204. DOI. © 2014 Elsevier Inc. Used with permission.

Recommended Citation

Wang, Lei; Wang, Feng; Fang, Wei; Johnson, Steven E.; Audi, Said H.; Zimmer, Michael; Holly, Thomas A.; Lee, Daniel C.; Zhu, Bao; Zhu, Haibo; and Zhao, Ming, "The Feasibility of Imaging Myocardial Ischemic/Reperfusion Injury Using ^99mTc-labeled Duramycin in a Porcine Model" (2015). Biomedical Engineering Faculty Research and Publications. 340.
https://epublications.marquette.edu/bioengin_fac/340