[68Ga]Annexin-V as a novel PET tracer for serial in-vivo monitoring of ischemia induced apoptosis in mice

Objectives [68Ga]-labelled Annexin-V as a novel PET tracer was evaluated for the in-vivo detection and monitoring of apoptosis after LAD-ligation in mice.

Methods Female mice (C57BL6/N) were anesthetized (1.5% Isofluran, 0.15 l O2 / min) and ligation of the LAD was performed after lateral thoracotomy. Dynamic PET was acquired on a Siemens Inveon P120 scanner over 90 minutes after i.v. injection of 15 MBq [68Ga]Annexin-V on days 1-6 after surgery, followed by a 30 minute [18F]-FDG landmarking scan. %ID/g was calculated by multiple ROI analyses and compared with the results of autoradiography and histology (TUNEL staining) after dissection of the hearts.

Results In-vivo PET delivered increasing [68Ga]Annexin-V uptake values in the infracted myocardium from day 1 (2.50 ± 1.10 %ID/g, n=4) to day 3 (2.80 ± 1.40 %ID/g, n=4). From day 4 to day 6 (1.48 % ID/g, n=4) decreasing uptake values were registered. Autoradiography likewise showed increasing tracer uptake in the infarcted region until day 3 (seven-fold the background activity of healthy myocardium), which subsequently returned to background values at day 6. There was an excellent correlation found with histology (TUNEL-staining), where 25% apoptotic cells were detected on day 1, a peak of 40% on day 3 and a decrease to 15% apoptotic cells on day 6.

Conclusions [68Ga]Annexin-V PET imaging is feasible for serial in-vivo imaging of ischemia induced myocardial apoptosis in mice and can potentially be used for monitoring novel anti-apoptotic therapies