In vivo imaging of metastatic breast cancer tumors at very early stages is on the verge of becoming possible. A team of chemists and biologists from the Center for Molecular Biophysics (CNRS) has indeed developed a new magnetic resonance imaging (MRI) probe that shows selective affinity for an emerging biomarker of metastatic breast cancer: Netrin-1.
Despite considerable progress in imaging and cancer treatment, methods for early diagnosis of metastasis detection and a better understanding of cancer progression remain a real clinical need. Molecular imaging can meet this need through "smart" contrast agents that target specific tumor biomarkers. A good candidate for breast cancer targeting is Netrin-1, an extracellular protein involved in tumor progression and aggressiveness, and the onset of metastases. This protein is overexpressed in metastatic breast cancer.
Chemists from the Center for Molecular Biophysics have recently designed, synthesized, and validated
in vivo a Netrin-1 specific probe. This probe is a peptide with high affinity for Netrin-1, modified by a gadolinium complex, a contrast agent commonly used in medical imaging. The structure of the probe was confirmed by molecular modeling thanks to a collaboration with the Institute of Organic and Analytical Chemistry (CNRS/University of Orleans).
This probe allowed researchers to very clearly visualize, by MRI, very small breast tumors (volume less than 50 mm
3). The signal intensity is three times more intense than that of DOTAREM, a reference contrast product used in MRI. This type of probe also allows imaging by single-photon emission tomography, using a radioactive metal instead of gadolinium.
A new contrast agent consisting of a peptide modified by a gadolinium complex allows early diagnosis of cancerous tumors through medical imaging.
© Sara Lacerda
This bimodal imaging approach, which covers a wide range of target concentrations (nanomolar to micromolar), has already enabled
in vivo mapping of Netrin-1 in murine models of cancer at different stages of tumor evolution. An advancement published in the journal
Bioconjugate Chemistry which, beyond early diagnosis, will also allow a better understanding of the development mechanisms of this type of cancer.
Writer: AVR
Reference:
Peptide-Conjugated MRI Probe Targeted to Netrin-1, a Novel Metastatic Breast Cancer Biomarker
Clémentine Moreau, Tea Lukačević, Agnès Pallier, Julien Sobilo, Samia Aci-Sèche, Norbert Garnier, Sandra Même, Éva Tóth & Sara Lacerda.
Bioconjugate Chemistry 2024
https://doi.org/10.1021/acs.bioconjchem.3c00558