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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Updated: Apr 13, 2026

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Heterogeneous Response After [ 177 Lu]Lu-FAPI-2286 Combination Therapy in Metastatic Breast Cancer.

Ghasemali Divband1, Masoume Chehrara2, Nastaran Khodakarim3

  • 1Jam Nuclear Medicine Center, Jam Hospital.

Clinical Nuclear Medicine
|January 12, 2026
PubMed
Summary
This summary is machine-generated.

This study explored radionuclide therapy targeting fibroblast activation protein (FAPI) in metastatic breast cancer. While showing initial promise with reduced tumor uptake and symptom relief, the therapy demonstrated a heterogeneous response with disease recurrence.

Keywords:
combination therapyfibroblast activation protein inhibitor (FAPI)metastatic breast cancertargeted radionuclide therapy

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Area of Science:

  • Oncology
  • Nuclear Medicine
  • Radiopharmaceutical Therapy

Background:

  • Metastatic invasive ductal carcinoma often develops resistance to standard therapies like anti-HER2 treatment.
  • Fibroblast Activation Protein (FAPI) is frequently overexpressed in various cancers, making it a potential therapeutic target.

Purpose of the Study:

  • To evaluate the efficacy and safety of [177Lu]Lu-FAPI-2286 radionuclide therapy combined with antibody-drug conjugate chemotherapy in a patient with metastatic invasive ductal carcinoma.
  • To assess the changes in FAPI expression and tumor burden following treatment.

Main Methods:

  • A patient with metastatic invasive ductal carcinoma, refractory to anti-HER2 therapy, received [177Lu]Lu-FAPI-2286 radionuclide therapy and chemotherapy.
  • Baseline [68Ga]Ga-FAPI-2286 PET/CT was performed to confirm FAPI expression.
  • Follow-up imaging and clinical assessment were conducted after 5 cycles of therapy.

Main Results:

  • Initial imaging revealed a significant reduction in FAPI uptake in skin lesions, resolution of bone lesions, and decreased pleural thickening.
  • The patient experienced clinical improvement, including pain relief and lymphedema resolution.
  • However, new metastatic lesions emerged in lymph nodes, indicating a heterogeneous treatment response and disease recurrence.

Conclusions:

  • [177Lu]Lu-FAPI-2286 radionuclide therapy combined with chemotherapy shows potential in managing metastatic breast cancer by reducing tumor burden and improving symptoms.
  • The emergence of new metastases highlights the need for further research into overcoming treatment resistance and addressing heterogeneous FAPI expression in advanced cancers.