68Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice

Increased expression of alpha v beta 3/alpha v beta 5 integrin is involved in angiogenesis and the inflammatory process in atherosclerotic plaques. The novel Ga-68-DOTA-RGD peptide binds with high affinity to alpha v beta 3/alpha v beta 5 integrin. The aim of this study was to investigate the uptake of the Ga-68-DOTA-RGD peptide in atherosclerotic plaques. Uptake of intravenously administered Ga-68-DOTA-RGD peptide was studied ex vivo in excised tissue samples and aortic sections of LDLR(-/-)ApoB(100/100) atherosclerotic mice. The uptake of the tracer in aortic cryosections was examined by using digital autoradiography. Subsequently, the autoradiographs were combined with histological and immunohistological analysis of the sections. DOTA-RGD peptide was successfully labelled with the generator-produced Ga-68. The tracer had reasonably good specific radioactivity (8.7 +/- 1.1 GBq/mu mol) and was quite stable in vivo. According to ex vivo biodistribution results, Ga-68-DOTA-RGD was cleared rapidly from the blood circulation and excreted through the kidneys to the urine with high radioactivity in the intestine, lungs, spleen and liver. Autoradiography results showed significantly higher uptake of Ga-68-DOTA-RGD peptide in the atherosclerotic plaques compared to healthy vessel wall (mean ratio +/- SD 1.4 +/- 0.1, p = 0.0004). We observed that Ga-68-DOTA-RGD is accumulated into the plaques of atherosclerotic mice. However, this data only shows the feasibility of the approach, while the clinical significance still remains to be proven. Further studies are warranted to assess the uptake of this tracer into human atherosclerotic plaques.