Clinical Translation of a 68Ga-Labeled Integrin αvβ6–Targeting Cyclic Radiotracer for PET Imaging of Pancreatic Cancer

The overexpression of integrin αvβ6 in pancreatic cancer makes it a promising target for noninvasive PET imaging. However, currently, most integrin αvβ6–targeting radiotracers are based on linear peptides, which are quickly degraded in the serum by proteinases. Herein, we aimed to develop and assess a 68Ga-labeled integrin αvβ6–targeting cyclic peptide (68Ga-cycratide) for PET imaging of pancreatic cancer. Methods: 68Ga-cycratide was prepared, and its PET imaging profile was compared with that of the linear peptide (68Ga-linear-pep) in an integrin αvβ6–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 68Ga-cycratide, and biodistribution and dosimetry were calculated. PET/CT imaging of 2 patients was performed to investigate the potential role of 68Ga-cycratide in pancreatic cancer diagnosis and treatment monitoring. Results: 68Ga-cycratide exhibited significantly higher tumor uptake than did 68Ga-linear-pep in BxPC-3 tumor–bearing mice, owing—at least in part—to markedly improved in vivo stability. 68Ga-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 68Ga-cycratide was comparable to 18F-FDG for diagnostic imaging and postsurgery tumor relapse monitoring. Conclusion: 68Ga-cycratide is an integrin αvβ6–specific PET radiotracer with favorable pharmacokinetics and a favorable dosimetry profile. 68Ga-cycratide is expected to provide an effective noninvasive PET strategy for pancreatic cancer lesion detection and therapy response monitoring.

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