Molecular imaging of myocardial ischemic memory in rat, using 99mTc-fucoidan
Mikail N1,2,3, Anizan N3, Louedec L2,3, Aerts J1,2,3, Al Shoukr F1,3, Michel JB2, Letourneur D2, Chauvierre C2, Le Guludec D1,2,3, Rouzet F1,2,3
1 Nuclear Medicine Department, Bichat-Claude Bernard Hospital; 2 LVTS (INSERM U1148) Team 4, Cardiovascular Bioengineering; 3 Fédération de Recherche en Imagerie Multimodale (FRIM)
- LVTS (Inserm U1148)
- Fédération de Recherche en Imagerie Multimodale (FRIM, Univ. Paris Diderot)
- Laboratoire de Bio-Ingénierie des Polymères, Université Paris 13.
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The retrospective identification of a remote acute coronary syndrome is a diagnostic challenge. Because adhesion molecules such as selectins persist on the endothelial surface after ischemia has resolved, they represent a tissue “imprint” of the prior ischemic event, referred to as ischemic memory. 99mTechnetium labelled Fucoidan (99mTc-fucoidan) is an imaging agent of selectins. In this study we aimed to evaluate the ability of 99mTc-fucoidan SPECT to detect myocardial ischemic memory in various settings regarding occlusion duration and reperfusion delay.
Transient myocardial ischemic events have been induced in male Wistar rats (duration from 20 min to 5 min). 99mTc-fucoidan SPECT was performed after reperfusion delays of 2h, 6h and 24h. Animals were then sacrificed and their heart explanted, followed by autoradiography, histology (hematoxylin-eosin staining) and immunostaining (P-selectin).
Visual detection of 99mTc-fucoidan myocardial uptake is presented in Table. Quantitative assemment of myocardial tracer uptake on SPECT acquisitions was (according to ischemia duration): 20 min= 2.3±0.4 [1.9-2.7]; 10min= 3.8±0.2 [3.5-4.0]; 5min= 2.2±0.4 [1.9-2.9]). Areas of 99mTc-fucoidan uptake matched with endothelial expression of P-selectin.
This study shows that brief coronary occlusions (5 minutes) followed by reperfusion durations up to 24 hours are associated with P-selectin endothelial expression, and detectable in vivo by 99mTc-fucoidan SPECT. Therefore, 99mTc-fucoidan is a promising agent for detection of ischemic memory. It will be soon available as a GMP radiolabelling kit for clinical translation.