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Are heterobivalent GRPR- and VPAC1R-bispecific radiopeptides suitable for efficient in vivo tumor imaging of prostate carcinomas?

Receptor-specific peptides labeled with positron emitters play an important role in the clinical imaging of several malignancies by positron emission tomography (PET). Radiolabeled heterobivalent bispecific peptidic ligands (HBPLs) can target more than one receptor type and by this - besides exhibit...

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Main Authors: Lindner, Simon (Author) , Rudolf, Henning (Author) , Palumbo, Giovanna (Author) , Oos, Rosel (Author) , Antons, Melissa Joy (Author) , Hübner, Ralph (Author) , Bartenstein, Peter (Author) , Schirrmacher, Ralf (Author) , Wängler, Björn (Author) , Wängler, Carmen (Author)
Format: Article (Journal)
Language:English
Published: 15 September 2021
In: Bioorganic & medicinal chemistry letters
Year: 2021, Volume: 48, Pages: 1-7
ISSN:1464-3405
DOI:10.1016/j.bmcl.2021.128241
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.bmcl.2021.128241
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0960894X21004686
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Author Notes:Simon Lindner, Henning Rudolf, Giovanna Palumbo, Rosel Oos, Melissa Antons, Ralph Hübner, Peter Bartenstein, Ralf Schirrmacher, Björn Wängler, Carmen Wängler
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Summary:Receptor-specific peptides labeled with positron emitters play an important role in the clinical imaging of several malignancies by positron emission tomography (PET). Radiolabeled heterobivalent bispecific peptidic ligands (HBPLs) can target more than one receptor type and by this - besides exhibiting other advantages - increase tumor imaging sensitivity. In the present study, we show the initial in vivo evaluation of the most potent heterobivalent gastrin-releasing peptide receptor (GRPR)- and vasoactive intestinal peptide receptor subtype 1 (VPAC1R)-bispecific radiotracer and determined its tumor visualization potential via PET/CT imaging. For this purpose, the most potent described HBPL was synthesized together with its partly scrambled heterobivalent monospecific homologs and its monovalent counterparts. The agents were efficiently labeled with 68Ga3+ and evaluated in an initial PET/CT tumor imaging study in a human prostate carcinoma (PCa) xenograft rat tumor model established for this purpose. None of the three 68Ga-HBPLs enabled a clear tumor visualization and a considerably higher involvement in receptor-mediated uptake was found for the GRPR-binding part of the molecule than for the VPAC1R-binding one. Of the monovalent radiotracers, only [68Ga]Ga-NODA-GA-PESIN could efficiently delineate the tumor, confirming the results. Thus, this work sets the direction for future developments in the field of GRPR- and VPAC1R-bispecific radioligands, which should be based on other VPAC1R-specific peptides than PACAP-27.
Item Description:Gesehen am 06.02.2023
Physical Description:Online Resource
ISSN:1464-3405
DOI:10.1016/j.bmcl.2021.128241

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