A novel urokinase plasminogen activator receptor-targeted peptide-based probe for in-vivo molecular imaging of glioblastoma. Issue 2 (16th February 2023)

• Record Type: Journal Article
• Authors: Han, Yunfeng; Tu, Le; Zhang, Yongxue; Xu, Liying; Sun, Ziyan
• Is Part Of: Nuclear medicine communications. Volume 44:Issue 2(2023)
• Page Start: 142
• Page End: 149
• Publication Date: 2023-02-16
• Subjects: glioma -- peptide-based imaging probe -- positron emission computed tomography imaging -- U87MG -- urokinase plasminogen activator receptor; Nuclear medicine -- Periodicals; 616.07575
• DOI: 10.1097/MNM.0000000000001644
• Languages: English
• ISSNs: 0143-3636

Abstract

Abstract : Aim: The urokinase plasminogen activator receptor (uPAR) is a promising biomarker for cancer diagnosis and therapy. We herein fabricated a new type of uPAR-targeted imaging probe Al 18 F-NOTA-VC and preliminarily evaluated its potential application in PET imaging of the glioma model in vivo. Methods: Peptide VC was synthesized and identified by MALDI-TOF-MS. The IC50 between VC/precursor NOTA-VC and uPAR was then determined before the synthesis and purification of Al 18 F-NOTA-VC, followed by further studies of in-vitro properties of Al 18 F-NOTA-VC. Meanwhile, the AE105-based probe followed a similar procedure in-vitro test. Finally, the PET imaging properties, including uPAR-targeting ability and the metabolism of Al 18 F-NOTA-VC, were investigated. Results: The VC and NOTA-VC were obtained successfully and demonstrated a good affinity with uPAR. Followed by Al 18 F labeling successfully, excellent properties, including the serum stability, water solubility, and specificity of Al 18 F-NOTA-VC, were obtained in-vitro test compared with AE105 based probe. An excellent tumor uptake and renal excretion data of Al 18 F-NOTA-VC were acquired from in-vivo U87MG tumor model PET imaging, consistent with the subsequent biodistribution study. Conclusion: In addition to the excellent specificity and high tumor/normal tissue contrast for uPAR-targeted PET imaging of U87MG tumor, Al 18 F-NOTA-VC possessed promising clearance ability by renal system route. These excellent properties facilitated Al 18 F-NOTA-VC to be a promising imaging agent for uPAR high-expressing tumors and, thus, provided a paradigm for developing peptide-based probes for uPAR-associated disease diagnosis.