Preparation and bioevaluation of [99mTc]Tc-labeled A7R and DA7R for SPECT imaging of triple-negative breast cancer. (31st October 2022)

• Record Type: Journal Article
• Authors: Su, Hongxing; Zhao, Lingzhou; Yu, Buhui; Zeng, Huahui; Yang, Jiqin; Zhu, Meilin; Zhao, Jinhua
• Is Part Of: New journal of chemistry. Volume 46:Number 44(2022)
• Page Start: 21401
• Page End: 21408
• Publication Date: 2022-10-31
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/d2nj04136g
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : [ 99m Tc]Tc-labeled D-type A7R peptide showed better tumor-to-muscle ratios and lower renal uptake. Abstract : Novel strategies for diagnosing triple-negative breast cancer (TNBC) are essential for effective clinical treatment. Vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1) are potential targets for tumor imaging agents. We designed and synthesized [ 99m Tc]Tc-labeled heptapeptide (A7R) and its D-type peptide ( D A7R) with high affinity and specificity for VEGFR2 and NRP-1 as novel single-photon emission computed tomography (SPECT) probes for TNBC imaging. The specificities of A7R and D A7R were first evaluated in vitro using flow cytometry and confocal microscopy and ex vivo using fluorescence imaging. Subsequently, A7R and D A7R were labeled with [ 99m Tc]Tc through 6-hydrazino nicotinamide (HYNIC), and their radiochemical purities (RCPs) and stability in vitro were assessed. The imaging performance and biodistribution of [ 99m Tc]Tc-HYNIC-A7R and [ 99m Tc]Tc-HYNIC- D A7R were evaluated in TNBC mouse models. A7R and D A7R exhibited good TNBC cell-targeting abilities and were readily labeled with [ 99m Tc]Tc through HYNIC. Both [ 99m Tc]Tc-HYNIC-A7R and [ 99m Tc]Tc-HYNIC- D A7R had high RCPs and stability in vitro, and their accumulation in tumor tissues in the TNBC models was evident, with fast blood clearance and favorable biodistribution. More importantly, [ 99m Tc]Tc-HYNIC- D A7R showed better tumor-to-muscle ratios and lower renal uptake than [ 99m Tc]Tc-HYNIC-A7R. These results suggest that both [ 99m Tc]Tc-HYNIC- D A7R and [ 99m Tc]Tc-HYNIC-A7R have substantial potential as probes for targeted SPECT imaging of TNBC, and the former may be considered for future clinical translation owing to its superior tumor imaging performance.