{"entity": "publication", "iuid": "e19fe20d31b842eb98d6c97cd7da68cb", "timestamp": "2026-09-24T05:14:46.785Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e19fe20d31b842eb98d6c97cd7da68cb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e19fe20d31b842eb98d6c97cd7da68cb"}}, "title": "Preclinical Validation of [177Lu]Lu-AKIR001, a CD44v6-Targeted Radiotherapeutic Entering First-in-Human Trials.", "authors": [{"family": "Mortensen", "given": "Anja C L", "initials": "ACL"}, {"family": "Mohajershojai", "given": "Tabassom", "initials": "T"}, {"family": "Gustafsson", "given": "Amanda", "initials": "A"}, {"family": "Berglund", "given": "Hanna", "initials": "H"}, {"family": "Selvaraju", "given": "Ram Kumar", "initials": "RK"}, {"family": "Hofstr\u00f6m", "given": "Camilla", "initials": "C"}, {"family": "Persson", "given": "Helena", "initials": "H"}, {"family": "Ohlin", "given": "Mats", "initials": "M"}, {"family": "Tran", "given": "Thuy A", "initials": "TA"}, {"family": "Mor\u00e9n", "given": "Anton Forsberg", "initials": "AF"}, {"family": "Ochniewicz", "given": "Piotr", "initials": "P"}, {"family": "Zedenius", "given": "Jan", "initials": "J"}, {"family": "Bernhardt", "given": "Peter", "initials": "P"}, {"family": "Frejd", "given": "Fredrik Y", "initials": "FY"}, {"family": "Nestor", "given": "Marika", "initials": "M"}], "type": "journal article", "published": "2026-02-02", "journal": {"title": "Journal of nuclear medicine : official publication, Society of Nuclear Medicine", "issn": "1535-5667", "volume": "67", "issue": "2", "pages": "269-275", "issn-l": "0161-5505"}, "abstract": "Targeted radionuclide therapy is an emerging potent therapeutic strategy in oncology. The cell surface antigen CD44v6 is a potential pan-cancer target for radionuclide therapy. This study aimed to evaluate the therapeutic efficacy, biodistribution, dosimetry, and safety profile of AKIR001, an antibody targeting CD44v6 labeled with 177Lu. Methods: The biodistribution and preclinical dosimetry of [177Lu]Lu-AKIR001 were calculated in the highly CD44v6-expressing A431 murine xenograft model, with subsequent extrapolation to predict human dosimetry. Therapeutic efficacy was evaluated across 3 xenograft models, 2 with high and 1 with moderate levels of CD44v6, using multiple dosing levels, fractionation regimens, and combinations with cisplatin. Preclinical toxicology was evaluated in a cross-reactive rabbit model and complemented by a PET imaging study using 68Ga-labeled AKIR001 in a cynomolgus macaque. Results: Biodistribution studies confirmed the high and selective tumor uptake of [177Lu]Lu-AKIR001, resulting in favorable dosimetry predictions for clinical application. Therapeutic evaluations demonstrated significant dose-dependent efficacy in all tested xenograft models, with fractionated dosing (2 doses) resulting in complete tumor regression in 80% of the animals in a radioresistant xenograft model. Biodistribution in rabbits demonstrated low uptake in normal tissues, and a good-laboratory-practice study using an excessive dose of AKIR001 was well tolerated, with no signs of adverse effects. PET imaging in a cynomolgus macaque corroborated these findings. Conclusion: Collectively, these data strongly support the therapeutic efficacy, safety, and dosimetry of [177Lu]Lu-AKIR001, justifying its advancement into clinical trials. A phase 1 clinical trial of [177Lu]Lu-AKIR001for CD44v6-positive solid cancers (NCT06639191) is currently recruiting patients.", "doi": "10.2967/jnumed.125.270782", "pmid": "41198237", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12866357"}, {"db": "pii", "key": "jnumed.125.270782"}, {"db": "ClinicalTrials.gov", "key": "NCT06639191"}], "notes": [], "created": "2026-09-23T11:35:54.584Z", "modified": "2026-09-23T11:35:54.623Z"}