Use of a Novel Arg-Gly-Asp Radioligand, F-18-AH111585, to Determine Changes in Tumor Vascularity After Antitumor Therapy

Despite the recent development of various radiolabeled Arg-Gly-Asp (RGD) peptides for imaging the alpha(v)beta(3) integrin receptor, relatively little attention has been focused on the ability of these radiotracers. to monitor changes in tumor vascularity after antitumor therapies. This study describes the favorable in vivo kinetics and tumor-targeting properties of F-18-AH111585, a novel F-18-RGD peptide, and its ability to monitor tumor vascularity noninvasively. Methods: Mice bearing Lewis lung carcinoma (LLC) tumors or Calu-6 non-small cell lung tumor xenografts were used for in vivo biodistribution and small-animal PET imaging studies. In addition, some animals were treated with either low-dose paclitaxel or the vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor ZD4190. Tumor uptake of F-18-AH111585 and microvessel density were then assessed. Results: Biodistribution of F-18-AH111585 demonstrated rapid clearance from the blood and key background organs and good tumor accumulation, with 1.5 percentage injected dose per gram (%ID/g) present at 2 h after injection in LLC tumors. Small-animal PET imaging of Calu-6 tumors allowed visualization of tumors above background tissue, with mean baseline uptake of 2.2 %ID/g. Paclitaxel therapy reduced the microvessel density in LLC tumor-bearing mice and resulted in significantly reduced F-18-AH111585 tumor uptake (P < 0.05). ZD4190 therapy resulted in a significant (31.8%) decrease in F-18-AH111585 uptake in Calu-6 tumors, compared with the vehicle control-treated Calu-6 tumors, which had a 26.9% increase in F-18-AH111585 uptake over the same period (P < 0.01). Conclusion: F-18-AH111585 is a promising F-18-labeled RGD tracer that offers a new approach to noninvasively image tumor vasculature. This tracer may reveal important information in the assessment of the impact of antitumor therapies, in particular those that predominantly target tumor blood vessels.