Pb-BCY20603

Pb-BCY20603 is a preclinical Bicycle Radionuclide Conjugate that links a high‑affinity MT1‑MMP–targeting bicyclic peptide to a chelate of the alpha‑emitting radioisotope lead‑212 for targeted alpha therapy of solid tumors overexpressing MT1‑MMP.[3][5][6] Developed by Bicycle Therapeutics in collaboration with Orano Med, the conjugate incorporates a reversible albumin‑binding half‑life–extension motif to improve pharmacokinetics, achieves high and homogeneous tumor uptake with tumor levels exceeding 45–50% injected dose per gram at 24 hours in rodent xenograft models, and induces potent antitumor activity and complete regressions in MT1‑MMP–positive xenografts at well‑tolerated dose levels.[3][5] Mechanistically, the bicyclic peptide component binds membrane type 1 matrix metalloproteinase (MT1‑MMP/MMP‑14) on tumor cells to selectively deliver 212Pb, whose alpha emissions cause clustered DNA double‑strand breaks and tumor cell killing, with an overall development focus on neoplasms.[3][5][6][8]

Other names

Bicycle Radionuclide Conjugate 212Pb-BCY20603BRC 212Pb-BCY20603BRC212Pb-BCY20603BRC-212Pb-BCY20603