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

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.