First-in-human study of 177Lu-EB-PSMA-617 in patients with metastatic castration-resistant prostate cancer

Eur J Nucl Med Mol Imaging. 2019 Jan;46(1):148-158. doi: 10.1007/s00259-018-4096-y. Epub 2018 Aug 8.

Abstract

Purpose: This translational study is designed to assess the safety, dosimetry and therapeutic response to a single, low-dose of 177Lu-EB-PSMA-617 in comparison to 177Lu-PSMA-617 in patients with mCRPC.

Methods: Following institutional review board approval and informed consent, nine patients with mCRPC were recruited. Four patients accepted intravenous injection of 0.80-1.1 GBq (21.5-30 mCi) of 177Lu-EB-PSMA-617, then underwent serial whole-body planar and SPECT/CT imaging at 2, 24, 72, 120 and 168 h. The other five patients accepted intravenous injection of 1.30-1.42 GBq (35-38.4 mCi) 177Lu-PSMA-617, then underwent the same imaging procedures at 0.5, 2, 24, 48, and 72 h. All patients were evaluated by 68Ga-PSMA-617 PET/CT before and one month after the treatment. Dosimetry evaluation was compared in both patient groups.

Results: When the bone metastasis tumors with comparable baseline SUVmax in the range of 10.0-15.0 were selected from the two groups for comparison, the accumulated radioactivity of 177Lu-EB-PSMA-617 was about 3.02-fold higher than that of 177Lu-PSMA-617. Imaging dose of 177Lu-EB-PSMA-617 treatment showed significant decrease of 68Ga-PSMA-617 uptake within a month, which was not observed in patients imaged with 177Lu-PSMA-617 (SUV change: -32.43 ± 0.14% vs. 0.21 ± 0.37%; P = 0.002). 177Lu-EB-PSMA-617 also had higher absorbed doses in the red bone marrow and kidneys than 177Lu-PSMA-617 (0.0547 ± 0.0062 vs. 0.0084 ± 0.0057 mSv/MBq for red bone marrow, P < 0.01; 2.39 ± 0.69 vs. 0.39 ± 0.06 mSv/MBq for kidneys, P < 0.01).

Conclusion: This first-in-human study demonstrated that 177Lu-EB-PSMA-617 had higher accumulation in mCRPC and that low imaging dose appears to be effective in treating tumors with high 68Ga-PSMA-617 uptakes. Elevated uptakes of 177Lu-EB-PSMA-617 in kidneys and red bone marrow were well tolerated at the administered low dose. Further investigations with increased dose and frequency of administration are warranted.

Keywords: 177Lu; Evans blue; Metastatic castration-resistant prostate cancer (mCRPC); Prostate-specific membrane antigen (PSMA); Radioligand therapy (RLT).

MeSH terms

  • Aged
  • Aged, 80 and over
  • Dipeptides / adverse effects
  • Dipeptides / pharmacokinetics*
  • Dipeptides / therapeutic use
  • Evans Blue
  • Heterocyclic Compounds, 1-Ring / adverse effects
  • Heterocyclic Compounds, 1-Ring / pharmacokinetics*
  • Heterocyclic Compounds, 1-Ring / therapeutic use
  • Humans
  • Lutetium
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prostate-Specific Antigen
  • Prostatic Neoplasms, Castration-Resistant / diagnostic imaging
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Prostatic Neoplasms, Castration-Resistant / radiotherapy*
  • Radiopharmaceuticals / adverse effects
  • Radiopharmaceuticals / pharmacokinetics*
  • Radiopharmaceuticals / therapeutic use
  • Single Photon Emission Computed Tomography Computed Tomography

Substances

  • 177Lu-EB-PSMA-617
  • 177Lu-PSMA-617
  • Dipeptides
  • Heterocyclic Compounds, 1-Ring
  • Radiopharmaceuticals
  • Evans Blue
  • Lutetium
  • Prostate-Specific Antigen