Clinical Translation of a Ga-Labeled Integrin αβ-Targeting Cyclic Radiotracer for PET Imaging of Pancreatic Cancer.

The overexpression of integrin αβ in pancreatic cancer makes it a promising target for noninvasive PET imaging. However, currently, most integrin αβ-targeting radiotracers are based on linear peptides, which are quickly degraded in the serum by proteinases. Herein, we aimed to develop and assess a Ga-labeled integrin αβ-targeting cyclic peptide (Ga-cycratide) for PET imaging of pancreatic cancer. Ga-cycratide was prepared, and its PET imaging profile was compared with that of the linear peptide (Ga-linear-pep) in an integrin αβ-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 Ga-cycratide, and biodistribution and dosimetry were calculated. PET/CT imaging of 2 patients was performed to investigate the potential role of Ga-cycratide in pancreatic cancer diagnosis and treatment monitoring. Ga-cycratide exhibited significantly higher tumor uptake than did Ga-linear-pep in BxPC-3 tumor-bearing mice, owing-at least in part-to markedly improved in vivo stability. 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 Ga-cycratide was comparable to F-FDG for diagnostic imaging and postsurgery tumor relapse monitoring. Ga-cycratide is an integrin αβ-specific PET radiotracer with favorable pharmacokinetics and a favorable dosimetry profile. Ga-cycratide is expected to provide an effective noninvasive PET strategy for pancreatic cancer lesion detection and therapy response monitoring.