{"entity": "publication", "iuid": "eb4af05d3d9d413c9e882a0e394f2850", "timestamp": "2026-08-26T22:47:02.295Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/eb4af05d3d9d413c9e882a0e394f2850.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/eb4af05d3d9d413c9e882a0e394f2850"}}, "title": "Enhancing the therapeutic effects of in vitro targeted radionuclide therapy of 3D multicellular tumor spheroids using the novel stapled MDM2/X-p53 antagonist PM2.", "authors": [{"family": "Mortensen", "given": "Anja C L", "initials": "ACL"}, {"family": "Morin", "given": "Eric", "initials": "E"}, {"family": "Brown", "given": "Christopher J", "initials": "CJ"}, {"family": "Lane", "given": "David P", "initials": "DP"}, {"family": "Nestor", "given": "Marika", "initials": "M"}], "type": "journal article", "published": "2020-04-16", "journal": {"title": "EJNMMI Res", "issn": "2191-219X", "volume": "10", "issue": "1", "pages": "38", "issn-l": "2191-219X"}, "abstract": "Precision therapeutics continuously make advances in cancer therapy, and a field of growing interest is the combination of targeted radionuclide therapy (TRNT) with potential radiosensitizing agents. This study evaluated whether the effects of in vitro TRNT, using the 177Lu-labeled anti-CD44v6 antibody AbN44v6, were potentiated by the novel stapled MDM2/X-p53 antagonist PM2.\n\nTwo wt p53 cell lines, HCT116 (colorectal carcinoma) and UM-SCC-74B (head and neck squamous cell carcinoma), expressing different levels of the target antigen, CD44v6, were used. Antigen-specific binding of 177Lu-AbN44v6 was initially verified in a 2D cell assay, after which the potential effects of unlabeled AbN44v6 on downstream phosphorylation of Erk1/2 were evaluated by western blotting. Further, the therapeutic effects of unlabeled AbN44v6, 177Lu-AbN44v6, PM2, or a combination (labeled/unlabeled AbN44v6 +/- PM2) were assessed in 3D multicellular tumor spheroid assays.\n\nRadiolabeled antibody bound specifically to CD44v6 on both cell lines. Unlabeled AbN44v6 binding did not induce downstream phosphorylation of Erk1/2 at any of the concentrations tested, and repeated treatments with the unlabeled antibody did not result in any spheroid growth inhibition. 177Lu-AbN44v6 impaired spheroid growth in a dose-dependent and antigen-dependent manner. A single modality treatment with 20 \u03bcM of PM2 significantly impaired spheroid growth in both spheroid models. Furthermore, the combination of TRNT and PM2-based therapy proved significantly more potent than either monotherapy. In HCT116 spheroids, this resulted in a two- and threefold spheroid growth rate decrease for the combination of PM2 and 100 kBq 177Lu-AbN44v6 compared to monotherapies 14-day post treatment. In UM-SCC-74B spheroids, the combination therapy resulted in a reduction in spheroid size compared to the initial spheroid size 10-day post treatment.\n\nTRNT using 177Lu-AbN44v6 proved efficient in stalling spheroid growth in a dose-dependent and antigen-dependent manner, and PM2 treatment demonstrated a growth inhibitory effect as a monotherapy. Moreover, by combining TRNT with PM2-based therapy, therapeutic effects of TRNT were potentiated in a 3D multicellular tumor spheroid model. This proof-of-concept study exemplifies the strength and possibility of combining TRNT targeting CD44v6 with PM2-based therapy.", "doi": "10.1186/s13550-020-0613-7", "pmid": "32300907", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7163001"}, {"db": "pii", "key": "10.1186/s13550-020-0613-7"}], "notes": [], "created": "2026-08-20T12:36:47.057Z", "modified": "2026-08-20T12:36:47.077Z"}