Issue 99, 2022

Validation of a post-radiolabeling bioconjugation strategy for radioactive rare earth complexes with minimal structural footprint

Abstract

The nine-coordinate aza-macrocycle DO3Apic-NO2 and its kinetically inert rare earth complexes [M(DO3A-pic-NO2)] (M = La, Tb, Eu, Lu, Y) can be readily bioconjugated to surface accessible thioles on peptides and proteins with a minimal structural footprint. All complexes express thioconjugation rate constants in the same order of magnitude (k = 0.3 h−1) with the exception of Sc (k = 0.89 h−1). Coupling to peptides and biologics with accessible cysteines also enables post-radiochelation bioconjugation at room temperature to afford injection-ready radiopharmaceuticals as demonstrated by formation of [177Lu][Lu(DO3Apic-NO2)] and [86Y][Y(DO3Apic-NO2)], followed by post-labeling conjugation to a cysteine-functionalized peptide targeting the prostate specific membrane antigen. The 86Y-labeled construct efficiently localizes in target tumors with no significant off-target accumulation as evidenced by positron emission tomography, biodistribution studies and metabolite analysis.

Graphical abstract: Validation of a post-radiolabeling bioconjugation strategy for radioactive rare earth complexes with minimal structural footprint

Supplementary files

Article information

Article type
Communication
Submitted
13 נוב 2022
Accepted
22 נוב 2022
First published
22 נוב 2022

Chem. Commun., 2022,58, 13728-13730

Author version available

Validation of a post-radiolabeling bioconjugation strategy for radioactive rare earth complexes with minimal structural footprint

R. Lengacher, A. G. Cosby, D. Śmiłowicz and E. Boros, Chem. Commun., 2022, 58, 13728 DOI: 10.1039/D2CC06128G

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