Abstract:

Background and purpose: Integrin α_vβ₃ receptor plays an important role in promoting, sustaining and regulating the angiogenesis. It is overexpressed on neovascular endothelial cells and tumor cells. RGD peptide specifically binds to integrin α_vβ₃, which could evaluate growth status and invasiveness of tumor. This study aimed to investigate the biodistribution in healthy KM mice and micro PET/CT imaging in U87MG tumor-bearing mice of ¹⁸F-E[c(RGDfK)₂]. Methods: ¹⁸F-E[c(RGDfK)2] was produced using an automated synthesis module via a simple one-step ¹⁸F-labeling strategy of the precursor 4-NO₂-3-TFMBz-E[c(RGDfK)₂]. The percentage activity of injection dose per gram of tissue (%ID/g) was calculated at 0.5, 1, 2, 4 h post injection of the probe. Micro PET/CT images of U87MG tumor-bearing nude mice with or without ¹⁸F-E[c(RGDfK)₂] blocking were acquired at each time point. Results: The labeling efficiency and radiochemical purity of ¹⁸F-E[c(RGDfK)₂] were 10% and 98%, respectively. ¹⁸F-E[c(RGDfK)₂] was excreted via renal route, with a high blood clearance. The other organs had backgroundlevel activity accumulation. At 1 h, the %ID/g of kidney, liver, intestine, muscle and blood was (1.02±0.16)%ID/g, (0.24±0.06)%ID/g, (0.35±0.03)%ID/g, (0.13±0.03)%ID/g and (0.11±0.03)%ID/g ¹⁸F-E[c(RGDfK)₂] had initial high tumor uptake [(5.2±0.56)%ID/g] and good tumor-to-background contrast (5.36) at 1 h post injection. Tumor uptake for blocking group was lower than those without blocking, and T/M reduced to 1.57. Conclusion: ¹⁸F-E[c(RGDfK)₂] appears a promising PET molecular imaging probe targeting integrin α_vβ₃, with high tumor uptake. It could be suitable for prognosis evaluation of integrin-positive tumor, selection of vascular targeting therapy and therapy effect monitoring.

Key words: ¹⁸F-E[c(RGDfK)₂], Integrin, Nude mice bearing U87MG human glioma xenogrfts, Micro PET/CT