Development of LRRC15-binding disulfide-constrained peptides for PET imaging of cancer-associated fibroblasts - PubMed
5 hours ago
- #PET Imaging
- #Cancer-Associated Fibroblasts
- #LRRC15
- LRRC15 is selectively expressed on cancer-associated fibroblasts (CAFs) and serves as a promising biomarker for tumor microenvironment imaging.
- Researchers developed disulfide-constrained peptides (DCPs), such as ML-YSD-07 and ML-PD-03, with subnanomolar affinity for murine LRRC15 using a combinatorial library and machine learning.
- PET imaging with 18F-radiolabeled ML-YSD-07 showed specific tumor accumulation in a murine pancreatic cancer model rich in LRRC15-expressing CAFs.
- Crystal structures reveal that DCPs adopt a distinct binding conformation interacting with a flat epitope on muLRRC15, highlighting LRRC15 as a valuable CAF biomarker for cancer imaging.
- Most authors were employees of Genentech, and some are inventors on a patent covering the peptides' design and uses, indicating potential commercial interests.