Molecular imaging of myocardial ischemic memory in rat, using ^99mTc-fucoidan

Mikail N^1,2,3, Anizan N³, Louedec L^2,3, Aerts J^1,2,3, Al Shoukr F^1,3, Michel JB², Letourneur D², Chauvierre C², Le Guludec D^1,2,3, Rouzet F^1,2,3

¹ Nuclear Medicine Department, Bichat-Claude Bernard Hospital; ² LVTS (INSERM U1148) Team 4, Cardiovascular Bioengineering; ³ Fédération de Recherche en Imagerie Multimodale (FRIM)

Partners :

• LVTS (Inserm U1148)
• Fédération de Recherche en Imagerie Multimodale (FRIM, Univ. Paris Diderot)
• Laboratoire de Bio-Ingénierie des Polymères, Université Paris 13.

Mail. : nidaa.mikail@gmail.com

Purpose:

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.

Methods:

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).

Results:

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.

Conclusion:

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.

Table