| Original language | English |
|---|
| Article number | 367 |
|---|
| Journal | Biomedicines |
|---|
| Volume | 9 |
|---|
| Issue number | 4 |
|---|
| Early online date | 1 Apr 2021 |
|---|
| DOIs | |
|---|
| Accepted/In press | 6 Mar 2021 |
|---|
| E-pub ahead of print | 1 Apr 2021 |
|---|
| Published | Apr 2021 |
|---|
| Additional links | |
|---|
Funding Information:
This project has received funding from the European Union?s Horizon 2020 research and innovation programme under grant agreement No 893784 and King?s Health Partners R&D Challenge Fund [MRC Confidence in concept (grant reference: MC_PC_17164)]. G.K and R.T.M.R. acknowledge funding from the EPSRC Centre for Doctoral Training in Medical Imaging [EP/L015226/1], Theragnostics Ltd., the Wellcome/EPSRC Centre for Medical Engineering [WT/203148/Z/16/Z], the EPSRC programme for next generation molecular imaging and therapy with radionuclides [EP/S032789/1], and a Wellcome Trust Multi User Equipment Grant: A multiuser radioanalytical facility for molecular imaging and radionuclide therapy research [WT/212885/Z/18/Z].
Funding Information:
Funding: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 893784 and King’s Health Partners R&D Challenge Fund [MRC Confidence in concept (grant reference: MC_PC_17164)]. G.K and R.T.M.R. acknowledge funding from the EPSRC Centre for Doctoral Training in Medical Imaging [EP/L015226/1], Therag-nostics Ltd., the Wellcome/EPSRC Centre for Medical Engineering [WT/203148/Z/16/Z], the EPSRC programme for next generation molecular imaging and therapy with radionuclides [EP/S032789/1], and a Wellcome Trust Multi User Equipment Grant: A multiuser radioanalytical facility for molecular imaging and radionuclide therapy research [WT/212885/Z/18/Z].
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
Hexadentate tris(3,4-hydroxypyridinone) ligands (THP) complex Fe3+ at very low iron concentrations and their high affinities for oxophilic trivalent metal ions have led to their development for new applications as bifunctional chelators for the radiometal gallium-68 (68Ga). THP-peptide bioconjugates rapidly and quantitatively complex 68Ga at room temperature, neutral pH, and micromolar ligand concentrations, making them amenable to kit-based radiosynthesis of 68Ga PET radiopharmaceuticals. With the aim to produce an N-hydroxysuccinimide-(NHS)-THP reagent for kit-based 68Ga-labeling and PET imaging, THP-derivatives were designed and synthesized to exploit the advantages of NHS chemistry for coupling with peptides, proteins, and antibodies. The more stable five-carbon atoms linker product was selected for a proof-of-concept conjugation and radiolabeling study with an anti-programmed death ligand 1 (PD-L1) camelid single domain antibody (sdAb) under mild conditions and further evaluated for site-specific amide bond formation with a synthesized glucagon-like peptide-1 (GLP-1) targeting peptide using solid-phase synthesis. The obtained THP-GLP-1 conjugate was tested for its 68Ga chelating ability, demonstrating to be a promising candidate for the detection and monitoring of GLP-1 aberrant malignancies. The obtained sdAb-THP conjugate was radiolabeled with 68Ga under mild conditions, providing sufficient labeling yields after 5 min, demonstrating that the novel NHS-THP bifunctional chelator can be widely used to easily conjugate the THP moiety to different targeting molecules (e.g., antibodies, anticalins, or peptides) under mild conditions, paving the way to the synthesis of different imaging probes with all the advantages of THP radiochemistry.