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

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Chemistry
• Oncology

Background:

• Human Epidermal growth factor Receptor 2 (HER2) is a key target in breast cancer.
• Developing high-affinity radioprobes is crucial for accurate HER2 detection in cancer imaging.

Purpose of the Study:

• To develop and evaluate a 99mTc-labeled HER2-specific molecular probe.
• To assess the impact of PEGylation on the probe's pharmacokinetic and biological properties.

Main Methods:

• Synthesis of two peptide variants: HYNIC-rL-A9 and HYNIC-PEG12-rL-A9.
• 99mTc-labeling using EDDA and tricine.
• In vitro cell uptake studies with SKBR3 cells.
• In vivo tumor uptake and blocking studies.

Main Results:

• PEGylated probe [99mTc]Tc-HYNIC-PEG12-rL-A9 showed high specific cellular uptake (3.01%) and low nanomolar binding affinity (Kd = 17.11 nM).
• Tumor uptake was higher for the PEGylated probe compared to the non-PEGylated version.
• Blocking studies confirmed the radiopeptide's specificity for HER2.

Conclusions:

• The PEGylated 99mTc-labeled rL-A9 peptide conjugate demonstrates improved biological characteristics.
• This probe is a promising candidate for accurate HER2-positive breast cancer detection.