ArticleClinical cancer research : an official journal of the American Association for Cancer Research2026
Exploring the 89Zr/177Lu Theranostic Pairing with an Extracellular Matrix-Targeted Radiopharmaceutical against Triple-Negative Breast Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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9 authors.
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Abstract
purposeTriple-negative breast cancer (TNBC) is highly aggressive and heterogeneous, with high rates of disease recurrence and poor treatment outcomes. The extra domain A of fibronectin is an extracellular matrix protein with high abundance in TNBC stroma and limited expression in healthy human tissues. Theranostic approaches have demonstrated improved patient outcomes by using identical targeting vectors for patient stratification through targeted positron emission tomography imaging and radioligand therapy; however, no radiopharmaceuticals are currently approved for TNBC. EXPERIMENTAL
design[89Zr]Zr-DFO-F8 (89Zr-F8) and [177Lu]Lu-CHX-A''-DTPA-F8 (177Lu-F8) were synthesized and characterized in vitro and in vivo for comparability in binding and biodistribution. Dosimetry estimation identified optimal dosing parameters for therapeutic benefit with limited off-target toxicities. 177Lu-F8 was assessed as a therapeutic against two TNBC xenograft mouse models. Weekly health and hematologic assessments with terminal serum chemistry and histopathology analysis were performed to evaluate toxicities.
results89Zr-F8 and 177Lu-F8 exhibited similar in vitro characteristics and similar tumor accumulation in two different xenografted mouse models of TNBC. 177Lu-F8 treatment significantly prolonged survival in both mouse models, with only transient myelosuppression and off-target myelotoxicity in Rag2-/- mice receiving the highest dose of the radiolabeled F8 antibody, as determined by blood measurements and terminal histopathology.
conclusionsThe zirconium-89/lutetium-177 theranostic nuclide coupling with the F8 delivery vector successfully identified TNBC xenografts and significantly extended the survival of xenografted mice.
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