Receptor-Targeted Peptide Conjugates Based on Diphosphines Enable Preparation of 99m Tc and 188 Re Theranostic Agents for Prostate Cancer.

Autor:	Pham TT; School of Bioengineering and Imaging Sciences, St. Thomas' Hospital, King's College London, London, United Kingdom; truc.pham@kcl.ac.uk michelle.ma@kcl.ac.uk., Hungnes IN; School of Bioengineering and Imaging Sciences, St. Thomas' Hospital, King's College London, London, United Kingdom., Rivas C; School of Bioengineering and Imaging Sciences, St. Thomas' Hospital, King's College London, London, United Kingdom., Cleaver J; Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, John Vane Science Centre, Queen Mary University of London, London, United Kingdom., Firth G; School of Bioengineering and Imaging Sciences, St. Thomas' Hospital, King's College London, London, United Kingdom., Blower PJ; School of Bioengineering and Imaging Sciences, St. Thomas' Hospital, King's College London, London, United Kingdom., Sosabowski J; Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, John Vane Science Centre, Queen Mary University of London, London, United Kingdom., Cook GJR; School of Bioengineering and Imaging Sciences, St. Thomas' Hospital, King's College London, London, United Kingdom., Livieratos L; School of Bioengineering and Imaging Sciences, St. Thomas' Hospital, King's College London, London, United Kingdom.; Department of Nuclear Medicine, Guy's and St. Thomas' Hospitals NHS Foundation Trust, Guy's Hospital, London, United Kingdom; and., Young JD; School of Bioengineering and Imaging Sciences, St. Thomas' Hospital, King's College London, London, United Kingdom.; Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, John Vane Science Centre, Queen Mary University of London, London, United Kingdom., Pringle PG; School of Chemistry, University of Bristol, Bristol, United Kingdom., Ma MT; School of Bioengineering and Imaging Sciences, St. Thomas' Hospital, King's College London, London, United Kingdom; truc.pham@kcl.ac.uk michelle.ma@kcl.ac.uk.
Jazyk:	angličtina
Zdroj:	Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2024 Jul 01; Vol. 65 (7), pp. 1087-1094. Date of Electronic Publication: 2024 Jul 01.
DOI:	10.2967/jnumed.124.267450
Abstrakt:	Benchtop 99 Mo/ 99m Tc and 188 W/ 188 Re generators enable economical production of molecular theranostic 99m Tc and 188 Re radiopharmaceuticals, provided that simple, kit-based chemistry exists to radiolabel targeting vectors with these radionuclides. We have previously described a diphosphine platform that efficiently incorporates 99m Tc into receptor-targeted peptides. Here, we report its application to label a prostate-specific membrane antigen (PSMA)-targeted peptide with 99m Tc and 188 Re for diagnostic imaging and systemic radiotherapy of prostate cancer. Methods: Two diphosphine-dipeptide bioconjugates, DP1-PSMAt and DP2-PSMAt, were formulated into kits for radiolabeling with 99m Tc and 188 Re. The resulting radiotracers were studied in vitro, in prostate cancer cells, and in vivo in mouse xenograft models, to assess similarity of uptake and biodistribution for each 99m Tc/ 188 Re pair of agents. Results: Both DP1-PSMAt and DP2-PSMAt could be efficiently radiolabeled with 99m Tc and 188 Re using kit-based methods to furnish the isostructural compounds M-DP1-PSMAt and M-DP2-PSMAt (M = [ 99m Tc]Tc, [ 188 Re]Re). All 99m Tc/ 188 Re radiotracers demonstrated specific uptake in PSMA-expressing prostate cancer cells, with negligible uptake in prostate cancer cells that did not express PSMA or in which PSMA uptake was blocked. M-DP1-PSMAt and M-DP2-PSMAt also exhibited high tumor uptake (18-30 percentage injected dose per gram at 2 h after injection), low retention in nontarget organs, fast blood clearance, and excretion predominantly via a renal pathway. Importantly, each pair of 99m Tc/ 188 Re radiotracers showed near-identical biologic behavior in these experiments. Conclusion: We have prepared and developed novel pairs of isostructural PSMA-targeting 99m Tc/ 188 Re theranostic agents. These generator-based theranostic agents have potential to provide access to the benefits of PSMA-targeted diagnostic imaging and systemic radiotherapy in health care settings that do not routinely have access to either reactor-produced 177 Lu radiopharmaceuticals or PET/CT infrastructure. (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)
Databáze:	MEDLINE
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