Pre-therapeutic dosimetry of normal organs and tissues of (177)Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer

Eur J Nucl Med Mol Imaging. 2015 Dec;42(13):1976-83. doi: 10.1007/s00259-015-3125-3. Epub 2015 Jul 31.

Abstract

Purpose: (177)Lu-617-prostate-specific membrane antigen (PSMA) ligand seems to be a promising tracer for radionuclide therapy of progressive prostate cancer. However, there are no published data regarding the radiation dose given to the normal tissues. The aim of the present study was to estimate the pretreatment radiation doses in patients who will undergo radiometabolic therapy using a tracer amount of (177)Lu-labeled PSMA ligand.

Methods: The study included seven patients with progressive prostate cancer with a mean age of 63.9 ± 3.9 years. All patients had prior PSMA positron emission tomography (PET) imaging and had intense tracer uptake at the lesions. The injected (177)Lu-PSMA-617 activity ranged from 185 to 210 MBq with a mean of 192.6 ± 11.0 MBq. To evaluate bone marrow absorbed dose 2-cc blood samples were withdrawn in short variable times (3, 15, 30, 60, and 180 min and 24, 48, and 120 h) after injection. Whole-body images were obtained at 4, 24, 48, and 120 h post-injection (p.i.). The geometric mean of anterior and posterior counts was determined through region of interest (ROI) analysis. Attenuation correction was applied using PSMA PET/CT images. The OLINDA/EXM dosimetry program was used for curve fitting, residence time calculation, and absorbed dose calculations.

Results: The calculated radiation-absorbed doses for each organ showed substantial variation. The highest radiation estimated doses were calculated for parotid glands and kidneys. Calculated radiation-absorbed doses per megabecquerel were 1.17 ± 0.31 mGy for parotid glands and 0.88 ± 0.40 mGy for kidneys. The radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands (p < 0.05). The calculated radiation dose to bone marrow was 0.03 ± 0.01 mGy/MBq.

Conclusion: Our first results suggested that (177)Lu-PSMA-617 therapy seems to be a safe method. The dose-limiting organ seems to be the parotid glands rather than kidneys and bone marrow. The lesion radiation doses are within acceptable ranges; however, there is a substantial individual variance so patient dosimetry seems to be mandatory.

Keywords: Castration resistant; Lu-177-PSMA; PSMA; Prostate cancer; Prostate specific membrane antigen; Radiometabolic therapy; Radionuclide treatment.

MeSH terms

  • Aged
  • Antigens, Surface
  • Bone Marrow / radiation effects
  • Dipeptides / administration & dosage
  • Dipeptides / therapeutic use*
  • Glutamate Carboxypeptidase II / antagonists & inhibitors*
  • Heterocyclic Compounds, 1-Ring / administration & dosage
  • Heterocyclic Compounds, 1-Ring / therapeutic use*
  • Humans
  • Kidney / radiation effects
  • Male
  • Middle Aged
  • Organs at Risk / radiation effects
  • Parotid Gland / radiation effects
  • Prostatic Neoplasms, Castration-Resistant / radiotherapy*
  • Radiopharmaceuticals / administration & dosage
  • Radiopharmaceuticals / adverse effects*
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use
  • Radiotherapy Dosage

Substances

  • 177Lu-PSMA-617
  • Antigens, Surface
  • Dipeptides
  • Heterocyclic Compounds, 1-Ring
  • Radiopharmaceuticals
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II