[68Ga]Ga-NODAGA-E[(cRGDyK)]2 angiogenesis PET following myocardial infarction in an experimental rat model predicts cardiac functional parameters and development of heart failure

BackgroundAngiogenesis has increasingly been a target for imaging and treatment over the last decade. The integrin alpha(v)beta(3) is highly expressed in cells during angiogenesis and are therefore a promising target for imaging. In this study, we aimed to investigate the PET tracer [Ga-68]Ga-RGD as a marker of angiogenesis following MI and its ability to predict cardiac functional parameters.MethodsFirst, the real-time interaction between [Ga-68]Ga-RGD and integrin alpha(v)beta(3) was investigated using surface plasmon resonance (SPR). Second, an animal study was performed to investigate the [Ga-68]Ga-RGD uptake in the infarcted area after one and four weeks following MI in a rat model (MI = 68, sham surgery = 36). Finally, the specificity of the [Ga-68]Ga-RGD tracer was evaluated ex vivo using histology, autoradiography, gamma counting and flow cytometry.ResultsSPR showed that [Ga-68]Ga-RGD has a high affinity for integrin alpha(v)beta(3), forming a strong and stable binding. PET/CT showed a significantly higher uptake of [Ga-68]Ga-RGD in the infarcted area compared to sham one week (p < 0.001) and four weeks (p < 0.001) after MI. The uptake of [Ga-68]Ga-RGD after one week correlated to end diastolic volume (r = 0.74, p < 0.001) and ejection fraction (r = - 0.71, p < 0.001) after four weeks.ConclusionThis study demonstrates that [Ga-68]Ga-RGD has a high affinity for integrin alpha(v)beta(3), which enables the evaluation of angiogenesis and remodeling. The [Ga-68]Ga-RGD uptake after one week indicates that [Ga-68]Ga-RGD may be used as an early predictor of cardiac functional parameters and possible development of heart failure after MI. These encouraging data supports the clinical translation and future use in MI patients.