Clinical Translation of a<sup>68</sup>Ga-Labeled Integrin α<sub>v</sub>β<sub>6</sub>–Targeting Cyclic Radiotracer for PET Imaging of Pancreatic Cancer
Xun Feng, Yanpu Wang, Dehua Lu, Xiaoxia Xu, Xin Zhou, Huiyuan Zhang, Ting Zhang, Hua Zhu, Zhi Yang, Fan Wang, Nan Li, Zhaofei Liu
Abstract
The overexpression of integrin α<sub>v</sub>β<sub>6</sub> in pancreatic cancer makes it a promising target for noninvasive PET imaging. However, currently, most integrin α<sub>v</sub>β<sub>6</sub>–targeting radiotracers are based on linear peptides, which are quickly degraded in the serum by proteinases. Herein, we aimed to develop and assess a <sup>68</sup>Ga-labeled integrin α<sub>v</sub>β<sub>6</sub>–targeting cyclic peptide (<sup>68</sup>Ga-cycratide) for PET imaging of pancreatic cancer. <b>Methods:</b><sup>68</sup>Ga-cycratide was prepared, and its PET imaging profile was compared with that of the linear peptide (<sup>68</sup>Ga-linear-pep) in an integrin α<sub>v</sub>β<sub>6</sub>–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 <sup>68</sup>Ga-cycratide, and biodistribution and dosimetry were calculated. PET/CT imaging of 2 patients was performed to investigate the potential role of <sup>68</sup>Ga-cycratide in pancreatic cancer diagnosis and treatment monitoring. <b>Results:</b><sup>68</sup>Ga-cycratide exhibited significantly higher tumor uptake than did <sup>68</sup>Ga-linear-pep in BxPC-3 tumor–bearing mice, owing—at least in part—to markedly improved in vivo stability. <sup>68</sup>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 <sup>68</sup>Ga-cycratide was comparable to <sup>18</sup>F-FDG for diagnostic imaging and postsurgery tumor relapse monitoring. <b>Conclusion:</b><sup>68</sup>Ga-cycratide is an integrin α<sub>v</sub>β<sub>6</sub>–specific PET radiotracer with favorable pharmacokinetics and a favorable dosimetry profile. <sup>68</sup>Ga-cycratide is expected to provide an effective noninvasive PET strategy for pancreatic cancer lesion detection and therapy response monitoring.