Shorter Peptide Nucleic Acid Probes Improve Affibody-Mediated Peptide Nucleic Acid-Based Pretargeting.

ABSTRACT: Affibody-mediated PNA-based pretargeting shows promise for HER2-expressing tumor radiotherapy. In our recent study, a 15-mer Z_HER2:342-HP15 affibody-PNA conjugate, in combination with a shorter 9-mer [¹⁷⁷Lu]Lu-HP16 effector probe, emerged as the most effective pretargeting strategy. It offered a superior tumor-to-kidney uptake ratio and more efficient tumor targeting compared to longer radiolabeled effector probes containing 12 or 15 complementary PNA bases. To enhance the production efficiency of our pretargeting system, we here introduce even shorter 6-, 7-, and 8-mer secondary probes, designated as HP19, HP21, and HP20, respectively. We also explore the replacement of the original 15-mer Z-HP15 primary probe with shorter 12-mer Z-HP12 and 9-mer Z-HP9 alternatives.

SUBMITTER: Westerlund K 

PROVIDER: S-EPMC11091976 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature