99mTc-HYNIC PEGylated Peptide Probe Targeting HER2-Expression in Breast Cancer

被引:0
作者
Yadav, Sushree Arpitabala [1 ]
Vats, V. Kusum [1 ,2 ]
Gupta, Sonal [1 ,3 ]
Repaka, Krishna Mohan [4 ]
Satpati, Drishty [1 ,2 ]
机构
[1] Bhabha Atom Res Ctr, Radiopharmaceut Div, Mumbai, India
[2] Homi Bhabha Natl Inst, Mumbai, India
[3] Mumbai Univ, KETs V G Vaze Coll, Mumbai, India
[4] Board Radiat & Isotope Technol, Mumbai, India
关键词
HER2; receptors; PEG; rL-A9; SKBR3; Technetium-99; m; OVEREXPRESSION; HER2;
D O I
10.1111/cbdd.70064
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Increased HER2 expression during breast cancer and its metastatic spread can be checked by specific probes having high affinity towards the target. This study aimed at developing 99mTc-labelled HER2-specific molecular probe for accurate detection. The two rL-A9 peptide variants, HYNIC-rL-A9 and HYNIC-PEG12-rL-A9 were manually synthesized by solid phase methodology. 99mTc-labelling of peptides was accomplished using EDDA and tricine as co-ligands. [99mTc]Tc-HYNIC-rL-A9 showed poor uptake in HER2-expressing human breast carcinoma SKBR3 cells whereas the PEGylated counterpart [99mTc]Tc-HYNIC-PEG12-rL-A9 demonstrated high specific cellular uptake (3.01% +/- 0.14%) and low nanomolar binding affinity (Kd = 17.11 +/- 7.63 nM). Tumour uptake (SKBR3) of [99mTc]Tc-HYNIC-PEG12-rL-A9 was higher at 1 and 3 h in comparison to the non-PEGylated radiopeptide. Blocking studies led to 70% reduction in accumulation of radioactivity in the tumour indicating specificity of the radiopeptide. Introduction of polyethylene glycol (PEG12) as pharmacokinetic modifier led to significantly improved biological profile of the [99mTc]Tc-HYNIC-labelled rL-A9 peptide conjugate.
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页数:7
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