177Lu-Labeled Prostate-Specific Membrane Antigen Radioligand Therapy of Metastatic Castration-Resistant Prostate Cancer: Safety and Efficacy

J Nucl Med. 2016 Jul;57(7):1006-13. doi: 10.2967/jnumed.115.168443. Epub 2016 Jan 21.


The objective of this study was to analyze the safety and efficacy of the (177)Lu-labeled DOTAGA-based prostate-specific membrane antigen (PSMA) ligand (177)Lu-DOTAGA-(I-y)fk(Sub-KuE) ((177)Lu-PSMA) in patients with metastatic castration-resistant prostate cancer (mCRPC).

Methods: Fifty-six mCRPC patients underwent PSMA radioligand therapy (RLT) with (177)Lu-PSMA. (68)Ga-PSMA-(N,N'-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid) ((68)Ga-PSMA) PET/CT was used for patient selection and follow-up after PSMA RLT. Hematologic status, renal function, and serum prostate-specific antigen levels were documented before and after therapy. Dosimetry was performed in 30 patients.

Results: (177)Lu-PSMA demonstrated high absorbed tumor doses (median, 3.3 mGy/MBq) compared with the levels in normal organs. Parotid glands received higher doses (1.3 mGy/MBq) than kidneys (0.8 mGy/MBq). All patients tolerated the therapy without any acute adverse effects. Except for mild reversible xerostomia in 2 patients, no long-term side effects were observed. There was a small but statistically significant reduction in erythrocyte and leukocyte counts; only the reduction in erythrocyte counts decreased slightly below the reference range. No thrombocytopenia occurred. The severity of pain was significantly reduced in 2 of 6 patients (33.3%). A decrease in prostate-specific antigen levels was noted in 45 of 56 patients (80.4%). Of 25 patients monitored for at least 6 mo after 2 or more PSMA RLT cycles, a molecular response evaluation ((68)Ga-PSMA PET/CT) revealed partial remission in 14, stable disease in 2, and progressive disease in 9 patients. Contrast-enhanced CT revealed partial remission in 5, stable disease in 13, and progressive disease in 7 patients. The median progression-free survival was 13.7 mo, and the median overall survival was not reached during follow-up for 28 mo.

Conclusion: PSMA RLT with (177)Lu-PSMA is feasible, safe, and effective in end-stage progressive mCRPC with appropriate selection and follow-up of patients by (68)Ga-PSMA PET/CT through application of the concept of theranostics.

Keywords: PSMA; radioligand therapy; theranostics.

MeSH terms

  • Aged
  • Antigens, Surface / adverse effects
  • Antigens, Surface / therapeutic use*
  • Cohort Studies
  • Dipeptides / therapeutic use
  • Disease-Free Survival
  • Edetic Acid / analogs & derivatives
  • Erythrocyte Count
  • Gallium Isotopes
  • Gallium Radioisotopes
  • Glutamate Carboxypeptidase II / adverse effects
  • Glutamate Carboxypeptidase II / therapeutic use*
  • Heterocyclic Compounds, 1-Ring / therapeutic use
  • Humans
  • Leukocyte Count
  • Lutetium
  • Male
  • Neoplasm Metastasis
  • Oligopeptides
  • Organometallic Compounds / therapeutic use
  • Pain / etiology
  • Pain / radiotherapy
  • Patient Selection
  • Positron-Emission Tomography
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant / diagnostic imaging
  • Prostatic Neoplasms, Castration-Resistant / radiotherapy*
  • Radiometry
  • Radiopharmaceuticals / adverse effects
  • Radiopharmaceuticals / therapeutic use*
  • Treatment Outcome


  • 177Lu-PSMA-617
  • Antigens, Surface
  • Dipeptides
  • Gallium Isotopes
  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • Oligopeptides
  • Organometallic Compounds
  • Radiopharmaceuticals
  • gallium 68 PSMA-11
  • Lutetium
  • Edetic Acid
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II
  • Prostate-Specific Antigen