Scintigraphic evaluation of therapeutic angiogenesis induced by VEGF-loaded chitosan nanoparticles in a rodent model of hindlimb ischemia

We examined the therapeutic effect of chitosan nanoparticles (CHI) incorporating vascular endothelial growth factor (VEGF) on hindlimb ischemia using single photon emission computed tomography (SPECT) perfusion imaging. Rats (n=24) were divided randomly into four groups of six: control, VEGF, CHI, and CHI incorporated with VEGF (CHI-VEGF). The right femoral artery was ligated to block blood flow, and SPECT perfusion images were obtained every week for 4 weeks. The morphology of the synthesized CHI was identified as a spherical shape with an even size distribution (range, 93–250 nm). The VEGF loading efficiency in CHI was 8.6±2.1%. Upon injection into the femoral artery, 17.6±8.2% of the 99m Tc-labeled CHI-VEGF administered remained in the ischemic lesion. The restoration of blood flow (ratio of ischemia to normal) measured by SPECT perfusion imaging was greater in animals treated with CHI-VEGF compared to that in the control ( p =0.028), VEGF ( p =0.010), and CHI ( p =0.011) groups. Administering CHI-VEGF had a significant therapeutic effect in a hindlimb ischemic rat model. 99m Tc gamma perfusion imaging was useful to study therapeutic angiogenesis.