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

Clin Nucl Med. 2021 Aug 1;46(8):641-646. doi: 10.1097/RLU.0000000000003667.

Abstract

Objectives: This study is set out to estimate the radiation-absorbed doses to normal organs and tumor tissue using low-dose 177Lu-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 177Lu-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 177Lu-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 177Lu-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.

MeSH terms

  • Adult
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / radiotherapy
  • Endopeptidases / metabolism*
  • Humans
  • Lutetium / chemistry*
  • Male
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Quinolines / chemistry
  • Quinolines / therapeutic use*
  • Radiation Dosage*
  • Radioisotopes / chemistry*
  • Radiometry
  • Radiotherapy Dosage
  • Safety*
  • Single Photon Emission Computed Tomography Computed Tomography

Substances

  • 68Ga-FAPI
  • Membrane Proteins
  • Quinolines
  • Radioisotopes
  • Lutetium
  • Lutetium-177
  • Endopeptidases
  • fibroblast activation protein alpha