Evaluation of HER2-specific peptide ligand for its employment as radiolabeled imaging probe.
Hadis HonarvarEnrica CalceNunzianna DotiEmma LangellaAnna OrlovaJos BuijsValentina D'AmatoRoberto BiancoMichele SavianoVladimir TolmachevStefania De LucaPublished in: Scientific reports (2018)
HER2 transmembrane receptor is an important target in immunotherapy treatment of breast and gastroesophageal cancer. Molecular imaging of HER2 expression may provide essential prognostic and predictive information concerning disseminated cancer and aid in selection of an optimal therapy. Radiolabeled low molecular weight peptide ligands are particularly attractive as probes for molecular imaging, since they reach and bind to the target and clear from non-target organs and blood stream faster than bulky antibodies. In this study, we evaluated a potential HER2-imaging probe, an A9 nonapeptide, derived from the trastuzumab-Fab portion. Its cellular uptake was investigated by mass spectrometry analysis of the cytoplasmic cellular extracts. Moreover, based on in-silico modeling, DTPA chelator was conjugated to N-terminus of A9. 111In-labeled A9 demonstrated nanomolar affinity to HER2-expressing BT474 cells and favorable biodistribution profile in NMRI mice. This study suggests that the peptide A9 represents a good lead candidate for development of molecular probe, to be used for imaging purposes and for the delivery of cytotoxic agents.
Keyphrases
- high resolution
- living cells
- mass spectrometry
- papillary thyroid
- quantum dots
- induced apoptosis
- squamous cell
- healthcare
- fluorescence imaging
- computed tomography
- small molecule
- squamous cell carcinoma
- epidermal growth factor receptor
- type diabetes
- stem cells
- cell cycle arrest
- signaling pathway
- single molecule
- adipose tissue
- cell death
- tyrosine kinase
- combination therapy
- mesenchymal stem cells
- climate change
- risk assessment
- endoplasmic reticulum stress
- oxidative stress
- molecular dynamics simulations
- gas chromatography
- replacement therapy
- pi k akt
- insulin resistance
- smoking cessation
- positron emission tomography
- high fat diet induced