A novel compound, ¹⁷⁷Lu-FAP-2286, is emerging as a potential new radioligand therapy. This peptide-based radioligand therapy targets fibroblast activation protein (FAP), a protein found in abundance on cancer-associated fibroblasts (CAFs) within the tumor microenvironment of many cancers, including advanced prostate cancers. Unlike most therapies that focus solely on tumor cells, this approach also attacks the supportive stromal cells that help prostate tumors grow, invade, and spread, offering a unique angle to tackle the disease.
The way ¹⁷⁷Lu FAP 2286 works is both precise and powerful. It uses a peptide that seeks out FAP, binding tightly to it and  ensuring minimal off-target effects. Attached to this peptide is lutetium-177, a radioactive isotope that emits beta-particles. These particles travel only a few millimeters, delivering a concentrated dose of radiation to FAP-expressing CAFs and nearby prostate cancer cells. This “crossfire effect” means the radiation can zap both the supportive cells and the tumor itself, potentially shrinking prostate tumors or slowing their growth. Preclinical studies, like those using FAP-expressing cell models, have shown that a single dose can significantly reduce tumor size, hinting at its potential for prostate cancer patients.

The ongoing LuMIERE study, a Phase 1/2 clinical trial is testing this therapy in patients with FAP-expressing solid tumors, including prostate cancer. Patients are first screened with 68Ga FAP 2286 PET/CT scans to confirm FAP expression in their tumors, ensuring the therapy is tailored to those most likely to benefit. For prostate cancer patients, this is critical because not all tumors express high levels of FAP, but those that do—particularly aggressive or metastatic cases—could see significant advantages.
Early trial data, shared at the 2022 European Association of Nuclear Medicine Congress, showed that patients with advanced cancers tolerated the therapy well, with mostly mild side effects like fatigue or nausea (grade 1 or 2). One patient with a rare cancer achieved a partial response, with no tumor growth for over a year after six doses of 3.7 GBq, and another with gallbladder cancer had stable disease after four cycles. While prostate cancer-specific results are still emerging, these findings suggest that ¹⁷⁷Lu-FAP-2286 could offer similar benefits, potentially stabilizing or reducing tumor burden in men with FAP-positive prostate cancer.

Dosimetry studies further highlight why this therapy could be a good fit for metastatic prostate cancer. The radiation from ¹⁷⁷Lu-FAP-2286 lingers in tumor sites, with bone metastases absorbing a mean of 3.0 Gy/GBq, which is particularly relevant for prostate cancer, where bone metastases are common. The kidneys and bone marrow, critical organs for older patients, receive much lower doses (1.0 Gy/GBq and 0.05 Gy/GBq, respectively), reducing the risk of long-term damage. This targeted delivery could mean effective tumor control without the harsh side effects that often burden prostate cancer patients.

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Clinical trial.