Heterodimeric Radiotracer Targeting PSMA and GRPR for Imaging of Prostate Cancer-Optimization of the Affinity towards PSMA by Linker Modification in Murine Model.
GRPR
PSMA
SPPS
heterodimer
molecular imaging
prostate cancer
Journal
Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003
Informations de publication
Date de publication:
01 Jul 2020
01 Jul 2020
Historique:
received:
08
06
2020
revised:
27
06
2020
accepted:
28
06
2020
entrez:
8
7
2020
pubmed:
8
7
2020
medline:
8
7
2020
Statut:
epublish
Résumé
Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR) are promising targets for molecular imaging of prostate cancer (PCa) lesions. Due to the heterogenic overexpression of PSMA and GRPR in PCa, a heterodimeric radiotracer with the ability to bind to both targets could be beneficial. Recently, our group reported the novel heterodimer BQ7800 consisting of a urea-based PSMA inhibitor, the peptide-based GRPR antagonist RM26 and NOTA chelator. The study reported herein, aimed to improve the affinity of BQ7800 towards PSMA by changing the composition of the two linkers connecting the PSMA- and GRPR-targeting motifs. Three novel heterodimeric analogues were synthesized by incorporation of phenylalanine in the functional linker of the PSMA-binding motif and/or shortening the PEG-linker coupled to RM26. The heterodimers were labeled with indium-111 and evaluated in vitro. In the competitive binding assay, BQ7812, featuring phenylalanine and shorter PEG-linker, demonstrated a nine-fold improved affinity towards PSMA. In the in vivo biodistribution study of [
Identifiants
pubmed: 32630176
pii: pharmaceutics12070614
doi: 10.3390/pharmaceutics12070614
pmc: PMC7408065
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Vetenskapsrådet
ID : 2019-00986
Organisme : Cancerfonden
ID : 2017/425
Références
Lancet. 2016 Jan 2;387(10013):70-82
pubmed: 26074382
J Biol Chem. 1990 Jul 15;265(20):12052-8
pubmed: 2164025
Q J Nucl Med Mol Imaging. 2015 Sep;59(3):241-68
pubmed: 26213140
Pharmaceutics. 2019 Jul 23;11(7):
pubmed: 31340483
J Nucl Med. 2017 Jan;58(1):75-80
pubmed: 27493272
Molecules. 2014 Jul 17;19(7):10455-72
pubmed: 25036155
J Nucl Med. 2018 May;59(5):803-808
pubmed: 29084827
J Nucl Med. 2016 Apr;57(4):557-62
pubmed: 26659347
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
J Nucl Med. 2017 Dec;58(12):1883-1884
pubmed: 28970333
Bioconjug Chem. 2018 Feb 21;29(2):410-419
pubmed: 29254329
Bioconjug Chem. 2016 Mar 16;27(3):737-51
pubmed: 26726823
J Nucl Med. 2018 Feb;59(2):177-182
pubmed: 28986509
Nucl Med Biol. 2014 Apr;41(4):355-63
pubmed: 24508213
Int J Mol Sci. 2014 Apr 10;15(4):6046-61
pubmed: 24727373
J Nucl Med. 2017 Sep;58(Suppl 2):17S-26S
pubmed: 28864607
Nucl Med Commun. 2019 Mar;40(3):278-286
pubmed: 30763290
Mol Imaging Biol. 2018 Aug;20(4):501-509
pubmed: 29256046
Pathol Oncol Res. 2009 Jun;15(2):167-72
pubmed: 18802790
Curr Top Med Chem. 2013;13(8):951-62
pubmed: 23590171
J Control Release. 2014 Aug 10;187:118-32
pubmed: 24878184
Clin Cancer Res. 2013 Oct 1;19(19):5434-43
pubmed: 23935037
Lancet Oncol. 2019 Mar;20(3):325-326
pubmed: 30713037
Eur Urol. 2017 Apr;71(4):618-629
pubmed: 27568654
Prostate. 2014 May;74(6):659-68
pubmed: 24464532
Cancers (Basel). 2019 Sep 14;11(9):
pubmed: 31540122
Bioconjug Chem. 2013 Jul 17;24(7):1144-53
pubmed: 23763444