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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.

SUBMITTER: Lengacher R

PROVIDER: S-EPMC9811989 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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

Lengacher Raphael R Cosby Alexia G AG Śmiłowicz Dariusz D Boros Eszter E

Chemical communications (Cambridge, England) 20221213 99

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 e ...[more]

PMID: 36426996

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Project description:The chemical footprint (ChF), which combines life cycle assessment (LCA) and quantitative risk assessment principles, shows promise for exploring localized toxicity impacts of manufacturing processes, which is not achievable with LCA alone. An updated ChF method was applied to the global annual production of a hard disk drive (HDD) rare-earth element (REE) magnet assembly, assuming a supply chain in East and Southeast Asia. Existing REE magnet assembly LCA inventories were combined with supplier manufacturing locations to create a cradle-to-gate spatial unit process inventory. Emissions from the electricity grid for each manufacturing site were downscaled to hydrobasins of interest using the Global Power Plant Database. The predicted no effect concentration (PNEC) was chosen as the ecotoxicity pollution boundary to determine the threshold for dilution of each chemical of concern (CoC) and to calculate the ChF. Finally, a high-resolution hydrological database provided volumes of the freshwater river reach draining each hydrobasin and was used to calculate the dilution capacity (DC), that is, the volume required to remain at or below the PNEC for each CoC. The total ChF of annual REE magnet assembly production was 6.91E12 m3 , with hotspots in watersheds in China and Thailand where REEs are processed and steel metalworking takes place. Metals were the primary CoCs, with cadmium and chromium(VI) comprising 77% of total ChF. Dilution factors ranged from 5E-09 to 9E + 03 of the DC of the waterbody, reflecting the spatial variability in both emissions and DC. An advanced ChF method was demonstrated for HDD REE magnets. Scoping is a key step required to reduce model complexity. The use of regionalized fate factors and standardized hydrological data sets improves the comparability of ChFs across hydrobasins. Additional work to combine data sets into readily available tools is needed to increase usability and standardization of the ChF method and promote wider adoption. Integr Environ Assess Manag 2023;19:272-283. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Dataset Information

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

Publications

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

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