Year: 2024
Type: article
Abstract: Targeted theranostics heavily rely on metal isotopes conjugated to antibodies. Single‐domain antibodies, known as nanobodies, are much smaller in size without compromising specificity and affinity. The conventional way of conjugating metals to nanobodies involves non‐specific modification of amino acid residues with bifunctional chelating agents. We demonstrate that mutagenesis of a single residue in a nanobody creates a triple cysteine motif that selectively binds bismuth which is, for example, used in targeted alpha therapy. Two mutations create a quadruple cysteine mutant specific for gallium and indium used in positron emission tomography and single‐photon emission computed tomography, respectively. Labelling is quantitative within a few minutes. The metal nanobodies maintain structural integrity and stability over weeks, resist competition from endogenous metal binders like glutathione, and retain functionality.
Source: Angewandte Chemie
Institution: Australian National University
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: Australian Research Council
OpenAlex ID: W4403933944