| Title | Clinical Translation of a Ga-68-Labeled Integrin alpha(v)beta(6)-Targeting Cyclic Radiotracer for PET Imaging of Pancreatic Cancer |
| Authors | Feng, Xun Wang, Yanpu Lu, Dehua Xu, Xiaoxia Zhou, Xin Zhang, Huiyuan Zhang, Ting Zhu, Hua Yang, Zhi Wang, Fan Lie, Nan Liu, Zhaofei |
| Affiliation | Peking Univ, Sch Basic Med Sci, Hlth Sci Ctr, Med Isotopes Res Ctr, Beijing, Peoples R China Peking Univ, Sch Basic Med Sci, Hlth Sci Ctr, Dept Radiat Med, Beijing, Peoples R China Peking Univ Canc Hosp & Inst, Dept Nucl Med, Minist Educ Beijing, Key Lab Carcinogenesis & Translat Res, Beijing, Peoples R China |
| Keywords | POSITRON-EMISSION-TOMOGRAPHY CYSTINE KNOT PEPTIDES ALPHA-V-BETA-6 INTEGRIN PHOTODYNAMIC THERAPY EXPRESSION |
| Issue Date | 1-Oct-2020 |
| Publisher | JOURNAL OF NUCLEAR MEDICINE |
| Abstract | The overexpression of integrin alpha(v)beta(6) in pancreatic cancer makes it a promising target for noninvasive PET imaging. However, currently, most integrin alpha(v)beta(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 Ga-68-labeled integrin alpha(v)beta(6)-targeting cyclic peptide (Ga-68-cycratide) for PET imaging of pancreatic cancer. Methods: Ga-68-cycratide was prepared, and its PET imaging profile was compared with that of the linear peptide (Ga-68-linear-pep) in an integrin alpha(v)beta(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 Ga-68-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: Ga-68-cycratide exhibited significantly higher tumor uptake than did Ga-68-linear-pep in BxPC-3 tumor-bearing mice, owing-at least in part-to markedly improved in vivo stability. Ga-68-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-68-cycratide was comparable to F-18-FDG for diagnostic imaging and postsurgery tumor relapse monitoring. Conclusion: 68Ga-cycratide is an integrin alpha(v)beta(6)-specific PET radiotracer with favorable pharmacokinetics and a favorable dosimetry profile. Ga-68-cycratide is expected to provide an effective noninvasive PET strategy for pancreatic cancer lesion detection and therapy response monitoring. |
| URI | http://hdl.handle.net/20.500.11897/593146 |
| ISSN | 0161-5505 |
| DOI | 10.2967/jnumed.119.237347 |
| Indexed | SCI(E) |
| Appears in Collections: | 基础医学院 北京肿瘤医院 |
