SPECT imaging of myocardial infarction using 99mTc-labeled C2A domain of synaptotagmin I in a porcine ischemia–reperfusion model

Fang, Wei; Wang, Feng; Ji, Shundong; Zhu, Xiaoguang; Meier, Heidi T.; Hellman, Robert S.; Brindle, Kevin M.; Davletov, Bazbek; Zhao, Ming

doi:10.1016/j.nucmedbio.2007.06.014

« Previous Next »Nuclear Medicine and Biology
Volume 34, Issue 8 , Pages 917-923, November 2007

SPECT imaging of myocardial infarction using ^99mTc-labeled C2A domain of synaptotagmin I in a porcine ischemia–reperfusion model

Wei Fang
- Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China
- W. Fang and F. Wang contributed equally to this work.
Feng Wang
- Nuclear Medicine Department, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing 210006, China
- W. Fang and F. Wang contributed equally to this work.
Shundong Ji
- Jiangsu Institute of Hematology, 1st Hospital of Suzhou University, Suzhou 215006, China
Xiaoguang Zhu
- Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, WI 53226, USA
Heidi T. Meier
- Clinical Veterinarian and Radiology Research, Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin, WI 53295, USA
Robert S. Hellman
- Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin, WI 53226, USA
Kevin M. Brindle
- MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, UK
Bazbek Davletov
- Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK
Ming Zhao
- Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, WI 53226, USA
- Corresponding author. Tel.: +1 414 456 4059; fax: +1 414 456 6512.

Received 14 December 2006; received in revised form 18 June 2007; accepted 25 June 2007. published online 03 September 2007.

Abstract

Introduction

The C2A domain of synaptotagmin I recognizes necrotic and apoptotic cells by binding to exposed anionic phospholipids. The goal is to explore the potential imaging utility of ^99mTc-labeled C2A in the detection of acute cardiac cell death in a porcine model that resembles human cardiovascular physiology.

Methods

Ischemia (20–25 min) was induced in pigs (M/F, 20–25 kg) using balloon angioplasty. ^99mTc-C2A-GST (n=7) or ^99mTc-BSA (n=2) was injected intravenously 1–2 h after reperfusion. Noninfarct animals were injected with ^99mTc-C2A-GST (n=4). SPECT images were acquired at 3 and 6 h postinjection. Cardiac tissues were analyzed to confirm the presence of cell death.

Results

Focal uptake was detected in five out of seven subjects at 3 h and in all infarct subjects at 6 h postinjection but not in infarct animals injected with ^99mTc-BSA or in noninfarct animals with ^99mTc-C2A-GST. Gamma counting of infarct versus normal myocardium yielded a 10.2±5.7-fold elevation in absolute radioactivity, with histologically confirmed infarction.

Conclusions

We present data on imaging myocardial cell death in the acute phase of infarction in pigs. C2A holds promise and warrants further development as an infarct-avid molecular probe.

Keywords: SPECT imaging, C2A domain, Myocardial infarction