Abstract
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Objectives To identify and validate 18F-RGD-K5, a click chemistry-derived RGD-containing tracer for imaging integrin αvβ3 expression in vivo.
Methods RGD-K5 binding affinity was determined by both a Biacore and a cell-binding assay using cRGDfK as the control. Metabolic stability analyses were carried out in athymic nude mice at 30 and 60 min post injection. Biodistribution of 18F-RGD-K5 was evaluated at several time points in U87MG tumor bearing aythmic mice. MicroPET imaging studies were also carried out in same U87MG mouse model capturing either static or dynamic images. cRGDyK was co-administered for blocking studies.
Results RGD-K5 binds to integrin αvβ3 (Kd=7.9 nM) and its selectivity towards integrin αvβ3 is 2.3x and 3.4x higher vs related integrins. RGD-K5 was non-cytotoxic up to 5 µM in LS174T, A172 and MRC5 cell lines. The pharmacokinetic results show limited uptake of the tracer at 2 hr post injection in various organs, with renal clearance being the predominant excretion pathway. In vivo metabolism analyses show that the tracer remains 98% intact 1 hr post injection. MicroPET imaging results show 18F-RGD-K5 has preferential tumor uptake in U87MG xenografts with a tumor/muscle (T/M) ratio of >5:1 after 2 hrs. Co-administration of cRGDyK depressed 18F-RGD-K5 uptake in U87MG tumors.
Conclusions 18F-RGD-K5 has favorable imaging qualities: it displays selective renal clearance, is metabolically stable, has a high T/M ratio and has a high specificity for the integrin αvβ3 receptor. 18F-RGD-K5 is a promising tracer for imaging integrin αvβ3 expression in vivo.
- © 2009 by Society of Nuclear Medicine