Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Synthesis and Characterisation of DOTA-Kisspeptin-10 as a Potential Gallium-68/Lutetium-177 Theranostic Radiopharmaceutical

Janke Kleynhans
ORCID logo ,
Robert Reeve
,
Cathryn HS Driver
ORCID logo ,
Biljana Marjanovic-Painter
,
Mike M Sathekge
ORCID logo ,
Jan Rijn Zeevaart
ORCID logo ,
Thomas Ebenhan
,
Robert P Millar
* ORCID logo
Version 1 : Received: 19 April 2024 / Approved: 22 April 2024 / Online: 23 April 2024 (11:24:27 CEST)

How to cite: Kleynhans, J.; Reeve, R.; Driver, C.H.; Marjanovic-Painter, B.; Sathekge, M.M.; Zeevaart, J.R.; Ebenhan, T.; Millar, R.P. Synthesis and Characterisation of DOTA-Kisspeptin-10 as a Potential Gallium-68/Lutetium-177 Theranostic Radiopharmaceutical. Preprints 2024, 2024041446. https://doi.org/10.20944/preprints202404.1446.v1 Kleynhans, J.; Reeve, R.; Driver, C.H.; Marjanovic-Painter, B.; Sathekge, M.M.; Zeevaart, J.R.; Ebenhan, T.; Millar, R.P. Synthesis and Characterisation of DOTA-Kisspeptin-10 as a Potential Gallium-68/Lutetium-177 Theranostic Radiopharmaceutical. Preprints 2024, 2024041446. https://doi.org/10.20944/preprints202404.1446.v1

Abstract

Kisspeptin (KISS1) and its cognate receptor (KISS1R) are implicated in the progression of various cancers. However, a theranostic radiopharmaceutical targeting the KISS1 receptor (KISS1R) has yet to be explored. A gallium-68 labelled kisspeptin-10 (KP10) has potential as a pan-tumor radiopharmaceutical for the detection of cancers. Furthermore, a lutetium-177 labelled KP10 could find therapeutic application in treating oncological diseases. We attached DOTA to the NH2-terminus of KP10 as we posited that this modification would not impair biological activity and showed that receptor stimulation of inositol phosphate accumulation in HEK293 transfected with the KISS1R gene was similar for KP10 and DOTA-KP10. We describe optimization of radiolabeling with gallium-68 and lutetium-177 and stability in serum, plasma, and whole blood. Pharmacokinetics was established with µPET/CT and ex vivo measurements. Dynamic studies with µPET/CT demonstrated that background clearance for the radiopharmaceutical was rapid with a blood half-life of 18 ± 3 minutes. DOTA-KP10 demonstrated preserved functionality at KISS1R and good blood clearance. These promising results advocate the further development of KP10 structures which have high binding affinity along with proteolytic resistance.

Keywords

Theranostics; Peptide Receptor Radionuclide Therapy (PRRT); antimetastatic; Radiopharmaceutical; Positron Emission Computed Tomography (PET); Pharmacokinetics; Pharmacodynamics; tumorigenesis

Subject

Biology and Life Sciences, Endocrinology and Metabolism

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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