Evaluation of a New <sup>177</sup>Lu-Labeled Somatostatin Analog for the Treatment of Tumors Expressing Somatostatin Receptor Subtypes 2 and 5.

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Download: Evaluation of a New 177 Lu-Labeled Somatostatin Analog for the Treatment of Tumors Expressing Somatostatin Receptor Subtypes 2 and 5.pdf (1132.30 [Ko])
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Serval ID
serval:BIB_A77CC199073C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Evaluation of a New <sup>177</sup>Lu-Labeled Somatostatin Analog for the Treatment of Tumors Expressing Somatostatin Receptor Subtypes 2 and 5.
Journal
Molecules
Author(s)
Mansi R., Nicolas G.P., Del Pozzo L., Abid K.A., Grouzmann E., Fani M.
ISSN
1420-3049 (Electronic)
ISSN-L
1420-3049
Publication state
Published
Issued date
11/09/2020
Peer-reviewed
Oui
Volume
25
Number
18
Pages
4155
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Targeted radionuclide therapy of somatostatin receptor (SST)-expressing tumors is only partially addressed by the established somatostatin analogs having an affinity for the SST subtype 2 (SST2). Aiming to target a broader spectrum of tumors, we evaluated the bis-iodo-substituted somatostatin analog ST8950 ((4-amino-3-iodo)-d-Phe-c[Cys-(3-iodo)-Tyr-d-Trp-Lys-Val-Cys]-Thr-NH <sub>2</sub> ), having subnanomolar affinity for SST2 and SST5, labeled with [ <sup>177</sup> Lu]Lu <sup>3+</sup> via the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). Human Embryonic Kidney (HEK) cells stably transfected with the human SST2 (HEK-SST2) and SST5 (HEK-SST5) were used for in vitro and in vivo evaluation on a dual SST2- and SST5-expressing xenografted mouse model. <sup>nat</sup> Lu-DOTA-ST8950 showed nanomolar affinity for both subtypes (IC <sub>50</sub> (95% confidence interval): 0.37 (0.22-0.65) nM for SST2 and 3.4 (2.3-5.2) for SST5). The biodistribution of [ <sup>177</sup> Lu]Lu-DOTA-ST8950 was influenced by the injected mass, with 100 pmol demonstrating lower background activity than 10 pmol. [ <sup>177</sup> Lu]Lu-DOTA-ST8950 reached its maximal uptake on SST2- and SST5-tumors at 1 h p.i. (14.17 ± 1.78 and 1.78 ± 0.35%IA/g, respectively), remaining unchanged 4 h p.i., with a mean residence time of 8.6 and 0.79 h, respectively. Overall, [ <sup>177</sup> Lu]Lu-DOTA-ST8950 targets SST2-, SST5-expressing tumors in vivo to a lower extent, and has an effective dose similar to clinically used radiolabeled somatostatin analogs. Its main drawbacks are the low uptake in SST5-tumors and the persistent kidney uptake.
Keywords
Lu-177, SST2, SST5, dual-tumor mouse model, neuroendocrine tumors, radiolabeled somatostatin analogs, targeted radionuclide therapy
Pubmed
Web of science
Open Access
Yes
Create date
19/09/2020 11:54
Last modification date
07/07/2021 6:11
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