Comparison of cyclic RGD peptides for α(v)β(3) integrin detection in a rat model of myocardial infarction

BACKGROUND: Expression of α(v)β(3) integrin is increased after myocardial infarction as part of the repair process. Increased expression of α(v)β(3) has been shown by molecular imaging with (18)F-galacto-RGD in a rat model. The (68)Ga-labelled RGD compounds (68)Ga-NODAGA-RGD and (68)Ga-TRAP(RGD)(3) have high specificity and affinity, and may therefore serve as alternatives of (18)F-galacto-RGD for integrin imaging. METHODS: Left coronary artery ligation was performed in rats. After 1 week, rats were imaged with [(13)N]NH(3), followed by (18)F-galacto-RGD, (68)Ga-NODAGA-RGD or (68)Ga-TRAP(RGD)(3) using a dedicated animal PET/CT device. Rats were killed, and the activity in tissues was measured by gamma counting. The heart was sectioned for autoradiography and histology. Immunohistochemistry was performed on consecutive sections using CD31 for the endothelial cells and CD61 for β(3) expression (as part of the α(v)β(3) receptor). RESULTS: In vivo imaging showed focal RGD uptake in the hypoperfused area of infarcted myocardium as defined with [(13)N]NH(3) scan. In autoradiography images, augmented uptake of all RGD tracers was observed within the infarct area as verified by the HE staining. The tracer uptake ratios (infarct vs. remote) were 4.7 ± 0.8 for (18)F-galacto-RGD, 5.2 ± 0.8 for (68)Ga-NODAGA-RGD, and 4.1 ± 0.7 for (68)Ga-TRAP(RGD)(3). The (68)Ga-NODAGA-RGD ratio was higher compared to (68)Ga-TRAP(RGD)(3) (p = 0.04), but neither of the (68)Ga tracers differed from (18)F-galacto-RGD (p > 0.05). The area of augmented (68)Ga-RGD uptake was associated with β(3) integrin expression (CD61). CONCLUSION: (68)Ga-NODAGA-RGD and (68)Ga-TRAP(RGD)(3) uptake was equally increased in the infarct area at 1 week post infarction as (18)F-galacto-RGD. These results show the potential of (68)Ga-labelled RGD peptides to monitor integrin expression as a part of myocardial repair and angiogenesis after ischaemic injury in vivo.