{"entity": "publication", "iuid": "bd47efada1fd4eed8de1aca84396fddb", "timestamp": "2026-09-01T08:31:31.000Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/bd47efada1fd4eed8de1aca84396fddb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/bd47efada1fd4eed8de1aca84396fddb"}}, "title": "177Lu-labeled PSMA targeting therapeutic with optimized linker for treatment of disseminated prostate cancer; evaluation of biodistribution and dosimetry.", "authors": [{"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Seitova", "given": "Kamila", "initials": "K"}, {"family": "Lundmark", "given": "Fanny", "initials": "F"}, {"family": "Bodenko", "given": "Vitalina", "initials": "V"}, {"family": "Oroujeni", "given": "Maryam", "initials": "M"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V"}, {"family": "Rosenstr\u00f6m", "given": "Ulrika", "initials": "U"}, {"family": "Orlova", "given": "Anna", "initials": "A"}], "type": "journal article", "published": "2023-09-27", "journal": {"title": "Front Oncol", "issn": "2234-943X", "volume": "13", "pages": "1221103", "issn-l": "2234-943X"}, "abstract": "Prostate specific membrane antigen (PSMA), highly expressed in metastatic castration-resistant prostate cancer (mCRPC), is an established therapeutic target. Theranostic PSMA-targeting agents are widely used in patient management and has shown improved outcomes for mCRPC patients. Earlier, we optimized a urea-based probe for radionuclide visualization of PSMA-expression in vivo using computer modeling. With the purpose to develop a targeting agent equally suitable for radionuclide imaging and therapy, the agent containing DOTA chelator was designed (BQ7876). The aim of the study was to test the hypothesis that 177Lu-labeled BQ7876 possesses target binding and biodistribution properties potentially enabling its use for radiotherapy.\n\nBQ7876 was synthesized and labeled with Lu-177. Specificity and affinity of [177Lu]Lu-BQ7876 to PSMA-expressing PC3-pip cells was evaluated and its processing after binding to cells was studied. Animal studies in mice were performed to assess its biodistribution in vivo, target specificity and dosimetry. [177Lu]Lu-PSMA-617 was simultaneously evaluated for comparison.\n\nBQ7876 was labeled with Lu-177 with radiochemical yield >99%. Its binding to PSMA was specific in vitro and in vivo when tested in antigen saturation conditions as well as in PSMA-negative PC-3 tumors. The binding of [177Lu]Lu-BQ7876 to living cells was characterized by rapid association, while the dissociation included a rapid and a slow phase with affinities KD1 = 3.8 nM and KD2 = 25 nM. The half-maximal inhibitory concentration for natLu-BQ7876 was 59 nM that is equal to 61 nM for natLu-PSMA-617. Cellular processing of [177Lu]Lu-BQ7876 was accompanied by slow internalization. [177Lu]Lu-BQ7876 was cleared from blood and normal tissues rapidly. Initial elevated uptake in kidneys decreased rapidly, and by 3 h post injection, the renal uptake (13 \u00b1 3%ID/g) did not differ significantly from tumor uptake (9 \u00b1 3%ID/g). Tumor uptake was stable between 1 and 3 h followed by a slow decline. The highest absorbed dose was in kidneys, followed by organs and tissues in abdomen.\n\nBiodistribution studies in mice demonstrated that targeting properties of [177Lu]Lu-BQ7876 are not inferior to properties of [177Lu]Lu-PSMA-617, but do not offer any decisive advantages.", "doi": "10.3389/fonc.2023.1221103", "pmid": "37829345", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10565663"}], "notes": [], "created": "2026-08-21T13:00:30.230Z", "modified": "2026-08-21T13:00:30.242Z"}