Monitoring In Vivo Performances of Protein-Drug Conjugates Using Site-Selective Dual Radiolabeling and Ex Vivo Digital Imaging.
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
12 05 2022
12 05 2022
Historique:
pubmed:
3
5
2022
medline:
18
5
2022
entrez:
2
5
2022
Statut:
ppublish
Résumé
In preclinical models, the development and optimization of protein-drug conjugates require accurate determination of the plasma and tissue profiles of both the protein and its conjugated drug. To this aim, we developed a bioanalytical strategy based on dual radiolabeling and ex vivo digital imaging. By combining enzymatic and chemical reactions, we obtained homogeneous dual-labeled anti-MMP-14 Fabs (antigen-binding fragments) conjugated to monomethyl auristatin E where the protein scaffold was labeled with carbon-14 (14C) and the conjugated drug with tritium (3H). These antibody-drug conjugates with either a noncleavable or a cleavable linker were then evaluated in vivo. By combining liquid scintillation counting and ex vivo dual-isotope radio-imaging, it was possible not only to monitor both components simultaneously during their circulation phase but also to quantify accurately their amount accumulated within the different organs.
Identifiants
pubmed: 35500280
doi: 10.1021/acs.jmedchem.2c00401
pmc: PMC9833330
mid: NIHMS1860675
doi:
Substances chimiques
Carbon Radioisotopes
0
Immunoconjugates
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6953-6968Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM141089
Pays : United States
Références
Angew Chem Int Ed Engl. 2021 Jun 14;60(25):13757-13777
pubmed: 33258535
Nat Biotechnol. 1999 Aug;17(8):780-3
pubmed: 10429243
Antibodies (Basel). 2021 Apr 19;10(2):
pubmed: 33921632
Nat Rev Drug Discov. 2017 May;16(5):315-337
pubmed: 28303026
Cancer Res. 2014 Oct 15;74(20):5700-10
pubmed: 25145670
MAbs. 2017 Jul;9(5):801-811
pubmed: 28406343
Biochemistry. 2012 Oct 30;51(43):8679-89
pubmed: 23083324
Bioanalysis. 2015;7(13):1605-17
pubmed: 26226310
Pharmaceuticals (Basel). 2020 Sep 14;13(9):
pubmed: 32937862
Drugs. 2019 Sep;79(13):1467-1475
pubmed: 31352604
Anal Chem. 2016 May 3;88(9):4979-86
pubmed: 27075639
Pharm Res. 2015 Nov;32(11):3470-9
pubmed: 25446773
Chem Biol. 2013 Feb 21;20(2):161-7
pubmed: 23438745
Bioconjug Chem. 2008 Jan;19(1):271-8
pubmed: 17988081
Bioconjug Chem. 2002 Jul-Aug;13(4):855-69
pubmed: 12121142
Lancet. 2019 Aug 31;394(10200):793-804
pubmed: 31478503
Angew Chem Int Ed Engl. 2015 Sep 1;54(36):10474-7
pubmed: 26371960
Proc Natl Acad Sci U S A. 2016 Dec 27;113(52):14970-14975
pubmed: 27965386
Cancer Res. 2004 Feb 15;64(4):1460-7
pubmed: 14973048
Pharmaceuticals (Basel). 2020 Dec 14;13(12):
pubmed: 33327644
Chem Soc Rev. 2019 Aug 12;48(16):4361-4374
pubmed: 31294429
Bioconjug Chem. 2014 Apr 16;25(4):656-64
pubmed: 24559399
Pharm Res. 2012 Sep;29(9):2354-66
pubmed: 22740180
Mol Imaging. 2018 Jan-Dec;17:1536012118801223
pubmed: 30370812
J Pharmacol Exp Ther. 2009 Sep;330(3):932-8
pubmed: 19498104
Chem Commun (Camb). 2021 Jul 6;57(54):6680-6683
pubmed: 34132265
Angew Chem Int Ed Engl. 2018 Jul 26;57(31):9744-9748
pubmed: 29862657
Oncotarget. 2019 Oct 22;10(58):6234-6244
pubmed: 31692898
Drug Metab Dispos. 2016 Jul;44(7):897-910
pubmed: 27122302
Artif Cells Nanomed Biotechnol. 2020 Dec;48(1):408-414
pubmed: 31913714
Nat Biotechnol. 2012 Jan 22;30(2):184-9
pubmed: 22267010
J Nucl Med. 2018 Sep;59(9):1461-1466
pubmed: 29728518
Nat Protoc. 2009;4(3):372-84
pubmed: 19247287
Clin Cancer Res. 2004 Oct 15;10(20):7063-70
pubmed: 15501986
Xenobiotica. 2019 Sep;49(9):1097-1105
pubmed: 30299189
Acc Chem Res. 2021 Mar 16;54(6):1465-1480
pubmed: 33622033
Nat Biotechnol. 2003 Jul;21(7):778-84
pubmed: 12778055
Chembiochem. 2017 Oct 5;18(19):1923-1927
pubmed: 28771896
Infect Immun. 2009 Mar;77(3):1083-90
pubmed: 19103766
Bioconjug Chem. 2017 May 17;28(5):1371-1381
pubmed: 28388844
Oncotarget. 2017 Jan 10;8(2):2781-2799
pubmed: 27835863
Crit Rev Oncol Hematol. 2019 May;137:57-83
pubmed: 31014516
Bioconjug Chem. 2011 Oct 19;22(10):1994-2004
pubmed: 21913715
J Clin Med. 2021 Mar 23;10(6):
pubmed: 33806916
Front Immunol. 2017 Oct 12;8:1287
pubmed: 29075266
Nat Biotechnol. 2008 Aug;26(8):925-32
pubmed: 18641636
J Immunol Methods. 2008 Mar 20;332(1-2):41-52
pubmed: 18230399
Bioconjug Chem. 2017 Jul 19;28(7):1826-1833
pubmed: 28662334
J Pharm Anal. 2020 Jun;10(3):209-220
pubmed: 32612867
Clin Cancer Res. 2012 Nov 1;18(21):5845-9
pubmed: 22962441
Proc Natl Acad Sci U S A. 1987 Oct;84(19):6654-8
pubmed: 3477796