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Developing PEGylated Reversed D‑Peptide as a Novel HER2-Targeted SPECT Imaging Probe for Breast Cancer Detection
journal contribution
posted on 2020-07-24, 14:37 authored by Shuaifan Du, Chuangwei Luo, Guangjie Yang, Hannan Gao, Yanpu Wang, Xiaoda Li, Huiyun Zhao, Qi Luo, Xiaotu Ma, Jiyun Shi, Fan WangHuman
epidermal growth factor receptor-2 (HER2)-enriched breast
cancer is characterized by strong invasiveness, high recurrence rate,
and poor prognosis. HER2-specific imaging can help screening right
patients for appropriate HER2-targeted therapies. Previously, we have
developed a 99mTc-labeled HER2-targeted H6 peptide for
SPECT imaging of breast cancer. However, the poor metabolic stability
and high gallbladder uptake hamper its clinical application. In this
study, a retro-inverso D-peptide of H6 (RDH6) was designed to increase
the metabolic stability. PEGylation was used to improve its water
solubility and in vivo pharmacokinetics. The results showed that the
D-amino acids in 99mTc-PEG4-RDH6 brought better
metabolic stability than 99mTc-PEG4-H6, thus
achieving higher tumor uptake. As the length of the PEG chain increases,
the hydrophilicity of the probes gradually increased, which may also
be the main cause for the decreased liver uptake. Compared with radiotracers
modified by PEG4 and PEG12, 99mTc-PEG24-RDH6 had a comparable tumor uptake and the lowest liver
radioactivity. The SPECT imaging demonstrated that 99mTc-PEG24-RDH6 could specifically distinguish HER2-positive tumors
from HER2-negative tumors with better imaging contrast, which thus
has the potential for clinical screening of HER2-positive breast patients.
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stabilityHER 2-targeted therapiestumor uptakeSPECT imagingHER 2-positive breast patients99 m Tc-labeled HER 2-targeted H 6 ...Novel HER 2-Targeted SPECT Imaging ...HER 2-positive tumorsHER 2-specific imaging99 m Tc-PEG 24HER 2-negative tumorsscreening right patientsBreast Cancer Detection Human epide...RDH 6PEG chain increases99 m Tc-PEG 4
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