Abstract
The overexpression of integrin α(v)β(6) in pancreatic cancer makes it a promising target for noninvasive PET imaging. However, currently, most integrin α(v)β(6)-targeting radiotracers are based on linear peptides, which are quickly degraded in the serum by proteinases. Herein, we aimed to develop and assess a (68)Ga-labeled integrin α(v)β(6)-targeting cyclic peptide ((68)Ga-cycratide) for PET imaging of pancreatic cancer. Methods:(68)Ga-cycratide was prepared, and its PET imaging profile was compared with that of the linear peptide ((68)Ga-linear-pep) in an integrin α(v)β(6)-positive BxPC-3 human pancreatic cancer mouse model. Five healthy volunteers (2 women and 3 men) underwent whole-body PET/CT imaging after injection of (68)Ga-cycratide, and biodistribution and dosimetry were calculated. PET/CT imaging of 2 patients was performed to investigate the potential role of (68)Ga-cycratide in pancreatic cancer diagnosis and treatment monitoring. Results:(68)Ga-cycratide exhibited significantly higher tumor uptake than did (68)Ga-linear-pep in BxPC-3 tumor-bearing mice, owing-at least in part-to markedly improved in vivo stability. (68)Ga-cycratide could sensitively detect the pancreatic cancer lesions in an orthotopic mouse model and was well tolerated in all healthy volunteers. Preliminary PET/CT imaging in patients with pancreatic cancer demonstrated that (68)Ga-cycratide was comparable to (18)F-FDG for diagnostic imaging and postsurgery tumor relapse monitoring. Conclusion:(68)Ga-cycratide is an integrin α(v)β(6)-specific PET radiotracer with favorable pharmacokinetics and a favorable dosimetry profile. (68)Ga-cycratide is expected to provide an effective noninvasive PET strategy for pancreatic cancer lesion detection and therapy response monitoring.