Targeting of the Cholecystokinin-2 Receptor with the Minigastrin Analog 177 Lu-DOTA-PP-F11N: Does the Use of Protease Inhibitors Further Improve In Vivo Distribution?

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
Alexander W SauterMelpomeni Fani

Abstract

Patients with metastatic medullary thyroid cancer (MTC) have limited systemic treatment options. The use of radiolabeled gastrin analogs targeting the cholecystokinin-2 receptor (CCK2R) is an attractive approach. However, their therapeutic efficacy is presumably decreased by their enzymatic degradation in vivo. We aimed to investigate whether the chemically stabilized analog 177Lu-DOTA-PP-F11N (177Lu-DOTA-(dGlu)6-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH2) performs better than reference analogs with varying in vivo stability, namely 177Lu-DOTA-MG11 (177Lu-DOTA-dGlu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) and 177Lu-DOTA-PP-F11 (177Lu-DOTA-(dGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2), and whether the use of protease inhibitors further improves CCKR2 targeting. First human data on 177Lu-DOTA-PP-F11N are also reported. Methods: In vitro stability of all analogs was assessed against a panel of extra- and intracellular endoproteases, whereas their in vitro evaluation was performed using the human MTC MZ-CRC-1 and the transfected A431-CCK2R(+) cell lines. Biodistribution without and with the protease inhibitors phosphoramidon and thiorphan was assessed 4 h after injection in MZ-CRC-1 and A431-CCK2R(+) dual xenografts. Autoradiography of 177Lu-DOTA-PP-F11N ...Continue Reading

References

Mar 1, 1988·Gastroenterology·M Deschodt-LanckmanG J Dockray
Jul 10, 2001·Surgical Endoscopy·M ProssH U Schulz
May 7, 2002·Nature Reviews. Cancer·Mikala Egeblad, Zena Werb
Nov 13, 2004·Cell Cycle·Johanna A Joyce, Douglas Hanahan
Sep 23, 2006·Nature Reviews. Cancer·Mona Mostafa Mohamed, Bonnie F Sloane
Apr 12, 2007·World Journal of Surgery·Jeffrey F Moley, Elizabeth A Fialkowski
May 30, 2008·European Journal of Nuclear Medicine and Molecular Imaging·Stephan GoodHelmut R Maecke
Apr 5, 2011·European Journal of Nuclear Medicine and Molecular Imaging·Peter LavermanOtto C Boerman
Apr 30, 2011·European Journal of Nuclear Medicine and Molecular Imaging·Meltem OcakClemens Decristoforo
Nov 30, 2013·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Berthold A NockMarion de Jong
Dec 11, 2014·The New England Journal of Medicine·Adam Timmis
Mar 27, 2015·Thyroid : Official Journal of the American Thyroid Association·Samuel A WellsUNKNOWN American Thyroid Association Guidelines Task Force on Medullary Thyroid Carcinoma
Nov 27, 2015·The Lancet. Diabetes & Endocrinology·Julien HadouxMartin Schlumberger
Sep 25, 2016·Cancer Treatment Reviews·Vinicius ErnaniTaofeek K Owonikoko
May 27, 2017·European Journal of Nuclear Medicine and Molecular Imaging·Murat Fani BozkurtStefano Fanti

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Citations

Feb 6, 2020·Pharmaceuticals·Christine Rangger, Roland Haubner
Nov 4, 2020·Journal of Clinical Medicine·Erika Grossrubatscher Nike Group
Feb 13, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Marco VeronaMattia Asti
May 4, 2021·Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists·Hao FuLibo Chen
Sep 15, 2019·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Christof RottenburgerDamian Wild
Dec 12, 2018·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Maximilian KlinglerElisabeth von Guggenberg
Dec 24, 2018·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Guillaume P NicolasMelpomeni Fani
Jun 27, 2020·Current Medicinal Chemistry·Maximilian KlinglerElisabeth Von Guggenberg
Apr 18, 2020·Journal of Medicinal Chemistry·Nathalie M GrobThomas L Mindt
Apr 18, 2020·Journal of Medicinal Chemistry·Nathalie M GrobThomas L Mindt

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