Objectives: Matrix metalloproteinases (MMPs) are essential for healing after myocardial infarction (MI). We evaluated myocardial accumulation of a novel ⁶⁸Ga-DOTA-TCTP-1 peptide targeting activated MMP-9 subtype after MI in rat.

Methods: MI was induced by permanent left coronary artery ligation in rats. Ex vivo autoradiography was performed 30 min after 43±7.6 MBq injection of ⁶⁸Ga-DOTA-TCTP-1 (Ujula et al. Bioconjug Chem 2010) at 7 d (n=7) and 4 wk (n=8) post-MI or after sham-operation (n=5, both time-points). The left ventricle (LV) was cut in serial short axis cryosections for autoradiography and histology.

Results: Average MI size was 47 and 41% of the LV circumference at 7 d and 4 wk, respectively. Autoradiography showed focally increased ⁶⁸Ga-DOTA-TCTP-1 uptake (p<0.01 vs. sham) in the infarcted area both 7 d and 4 wk (MI-to-remote ratio 2.5±0.5 and 3.1±1.0, respectively). Double immunohistochemistry showed strong MMP-9 expression in scattered cells in the infarct area that co-localized with CD68 staining of macrophages. ⁶⁸Ga-DOTA-TCTP-1 uptake correlated with the amount of CD68 positive macrophages (r_s=0.91, p<0.001) in the scar. However, there was no correlation with collagen density (Masson trichrome) or capillary density (CD31 staining). Blood radioactivity remained high (blood-to-heart ratio 0.42±0.12) precluding in vivo imaging in this model.

Conclusions: ⁶⁸Ga-DOTA-TCTP-1, a novel tracer targeting specifically MMP-9 subtype activation, accumulates in the MI scar in the rat heart. Its uptake correlated with macrophage infiltration suggesting that the tracer may be useful for the detection of myocardial inflammation after MI.