Evaluation of 99mtc-peptide-zher2:342 affibody ? molecule for in vivo molecular imaging

摘要

Objective: The aim of this study was to develop an improved method for labelling ZHER2:342 with Technetium-99m (99mTc) using Gly-(D) Ala-Gly-Gly as a chelator and to evaluate the feasibility of its use for visualization of HER2 expression in vivo. Methods: The Affibody? molecule ZHER2:342 was synthesized by Fmoc/tBu solid phase synthesis. The chelator, Gly-(D) Ala-Gly-Gly, was introduced by manual synthesis as the N-terminal extensions of ZHER2:342. ZHER2:342 was labelled with 99mTc. The labelling efficiency, radiochemical purity and in vitro stability of the labelled molecular probe were analysed by reversed-phase high performance liquid chromatography. Biodistribution and molecular imaging using 99mTc-peptide-ZHER2:342 were performed. Results: The molecular probe was successfully synthesized and labelled with 99mTc with the labelling efficiency of 98.1061.73% (n55). The radiolabelled molecular probe remained highly stable in vitro. The molecular imaging showed high uptake in HER2-expressing SKOV- 3 xenografts, whereas the MDA-MB-231 xenografts with low HER2 expression were not clearly imaged at any time after the injection of 99mTc-peptide-ZHER2:342. The predominant clearance pathway for 99mTc-peptide-ZHER2:342 was through the kidneys. Conculsion: 99mTc-peptide-ZHER2:342 using Gly-(D) Ala-Gly-Gly as a chelator is a promising tracer agent with favourable biodistribution and imaging properties that may be developed as a radiopharmaceutical for the detection of HER2-positive malignant tumours. Advances in knowledge: The 99mTc-peptide-ZHER2:342 molecular probe is a promising tracer agent, and the results in this study provide a foundation for future development of protocols for earlier visual detection of cancer in the clinical setting.