- CEND-1 (iRGD) is a bifunctional cyclic peptide that can modulate the solid tumour microenvironment, enhancing the delivery and therapeutic index of co-administered anti-cancer agents. This study explored CEND-1’s pharmacokinetic (PK) properties pre-clinically and clinically, and assessed CEND-1 distribution, tumour selectivity and duration of action in pre-clinical tumour models. Its PK properties were assessed after intravenous infusion of CEND-1 at various doses in animals (mice, rats, dogs and monkeys) and patients with metastatic pancreatic cancer. To assess tissue disposition, [3H]-CEND-1 radioligand was administered intravenously to mice bearing orthotopic 4T1 mammary carcinoma, followed by tissue measurement using quantitative whole-body autoradiography or quantitative radioactivity analysis. The duration of the tumour-penetrating effect of CEND-1 was evaluated by assessing tumour accumulation of Evans blue and gadolinium-based contrast agents in hepatocellular carcinoma (HCC) mouse models. The plasma half-life was approximately 25 min in mice and 2 h in patients following intravenous administration of CEND-1. [3H]-CEND-1 localised to the tumour and several healthy tissues shortly after administration but was cleared from most healthy tissues by 3 h. Despite the rapid systemic clearance, tumours retained significant [3H]-CEND-1 several hours post-administration. In mice with HCC, the tumour penetration activity remained elevated for at least 24 h after the injection of a single dose of CEND-1. These results indicate a favourable in vivo PK profile of CEND-1 and a specific and sustained tumour homing and tumour penetrability. Taken together, these data suggest that even single injections of CEND-1 may elicit long-lasting tumour PK improvements for co-administered anti-cancer agents.
MetadatenAuthor: | Harri A. JärveläinenORCiD, Jens Christian Johannes SchmithalsGND, Maike von HartenGND, Bianca KakoschkyGND, Thomas J. VoglORCiDGND, Stephen HarrisORCiD, Claire Henson, Gemma Bullen-Clerkson, Albrecht PiiperORCiD |
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URN: | urn:nbn:de:hebis:30:3-868534 |
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DOI: | https://doi.org/10.3390/ijms24065700 |
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ISSN: | 1422-0067 |
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Parent Title (English): | International journal of molecular sciences |
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Publisher: | Molecular Diversity Preservation International |
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Place of publication: | Basel |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2023/03/16 |
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Date of first Publication: | 2023/03/16 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2024/09/18 |
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Tag: | CEND-1; LSTA1; certepetide; iRGD peptide; pharmacokinetics; quantitative radioactivity analysis (QRA); quantitative whole-body autoradiography (QWBA) |
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Volume: | 24 |
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Issue: | 6, art. 5700 |
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Article Number: | 5700 |
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Page Number: | 17 |
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First Page: | 1 |
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Last Page: | 17 |
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Note: | Funding: Cend Therapeutics, Inc. |
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Note: | Funding: DrugCendR Australia Pty Ltd. |
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Note: | Funding: Deutsche Krebshilfe ; 7011950 |
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Note: | Gefördert durch den Open-Access-Publikationsfonds der Goethe-Universität. |
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HeBIS-PPN: | 523176767 |
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Institutes: | Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Open-Access-Publikationsfonds: | Medizin |
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Licence (German): | Creative Commons - CC BY - Namensnennung 4.0 International |
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