Publication

Exploring the 89 Zr/ 177 Lu Theranostic Pairing with an Extracellular Matrix Targeted Radiopharmaceutical Against Triple Negative Breast Cancer.

2026

Abstract

Purpose. Triple 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 (EDA-FN) 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 utilizing identical targeting vectors for patient stratification by targeted positron emission tomography imaging and radioligand therapy, however no targeted radiopharmaceuticals are currently approved for TNBC. Experimental Design. [89Zr]Zr-DFO-F8 and [177Lu]Lu-CHX-A’’-DTPA-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]Lu-CHX-A’’-DTPA-F8 was assessed as a therapeutic against two triple negative breast cancer xenograft mouse models. Weekly health and hematological assessment with terminal serum chemistry and histopathology analysis was performed to evaluate toxicities. Results. [89Zr]Zr-DFO-F8 and [177Lu]Lu-CHX-A’’-DTPA-F8 exhibited similar in vitro characteristics, and similar tumor accumulation in two different xenografted mouse models of triple negative breast cancer. [177Lu]Lu-CHX-A’’-DTPA-F8 treatment significantly prolonged survival in both mouse models with only transient myelosuppression and off-target myelotoxicity only in Rag2-/- mice receiving the highest dose of radiolabeled F8 antibody, as determined by blood measurements and terminal histopathology. Conclusion. The 89Zr/177Lu theranostic nuclide coupling successfully identified triple negative breast cancer xenografts, and significantly extended survival of xenografted mice.

Official source

https://infoscience.epfl.ch/entities/publication/89d0ab89-3df1-4010-919f-3116e44befa1

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2026

Abstract

Official source

https://infoscience.epfl.ch/entities/publication/89d0ab89-3df1-4010-919f-3116e44befa1

About this result

Related concepts (32)

Positron emission tomography

Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, regional chemical composition, and absorption. Different tracers are used for various imaging purposes, depending on the target process within the body. For example, -FDG is commonly used to detect cancer, NaF is widely used for detecting bone formation, and oxygen-15 is sometimes used to measure blood flow.

Metastatic breast cancer

Metastatic breast cancer, also referred to as metastases, advanced breast cancer, secondary tumors, secondaries or stage IV breast cancer, is a stage of breast cancer where the breast cancer cells have spread to distant sites beyond the axillary lymph nodes. There is no cure for metastatic breast cancer; there is no stage after IV. Metastases can occur several years after the primary breast cancer, although it is sometimes diagnosed at the same time as the primary breast cancer or, rarely, before the primary breast cancer has been diagnosed.

Therapeutic index

The therapeutic index (TI; also referred to as therapeutic ratio) is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity. The related terms therapeutic window or safety window refer to a range of doses optimized between efficacy and toxicity, achieving the greatest therapeutic benefit without resulting in unacceptable side-effects or toxicity.

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