Safety of Fibroblast Activation Protein–Targeted Radionuclide Therapy by a Low-Dose Dosimetric Approach Using 177Lu-FAPI04

Objectives This study is set out to estimate the radiation-absorbed doses to normal organs and tumor tissue using low-dose 177 Lu-FAPI04 dosimetry to determine the safety and theranostic potential of fibroblast activation protein–targeted radionuclide therapy. Patients and Methods Four patients with metastatic advanced-stage cancer were administered low-dose 177 Lu-FAPI04 for dosimetry measurements. Data acquisition for dosimetry of normal organs and tumors was performed by whole-body and 3D SPECT/CT imaging at 4, 24, 48, and 96 hours after administering 177 Lu-FAPI04. Blood samples were drawn at 5, 15, 30, 60, 60, 120, and 180 minutes, and at 24, 48, and 96 hours for bone marrow dosimetry calculations. Results Mean absorbed doses per megabecquerel were 0.25 ± 0.16 mGy (range, 0.11–0.47 mGy), 0.11 ± 0.08 mGy (range, 0.06–0.22 mGy), and 0.04 ± 0.002 mGy (range, 0.04–0.046 mGy) for kidneys, liver, and bone marrow, respectively. The respective maximum estimated amount of radioactivity to reach radiation-absorbed dose limits were 120.9 ± 68.6 GBq, 47.5 ± 2.8 GBq, 397.8 ± 217.1 GBq, and 52.4 ± 15.3 GBq for kidneys, bone marrow, liver, and total body. The mean absorbed dose per megabecquerel was 0.62 ± 0.55 mGy for bone metastases, 0.38 ± 0.22 mGy for metastatic lymph nodes, 0.33 ± 0.21 mGy for liver metastases, and 0.37 ± 0.29 for metastatic soft tissue. The maximum absorbed dose in a tumor lesion was 1.67 mGy/MBq for bone, 0.6 mGy/MBq for lymph node, 0.62 mGy/MBq for liver, and 1 mGy/MBq for soft tissue. Conclusions The mean absorbed dose to organs at risk with 177 Lu-FAPI04 is reasonably low, allowing for low tumor-absorbed dose rates by administering a higher dose. Further research on optimizing therapeutic efficacy and using alternative radioisotopes is necessary, along with an individualized dosimetric approach.