Dosimetry of 177Lu-PSMA-617 after Mannitol Infusion and Glutamate Tablet Administration: Preliminary Results of EUDRACT/RSO 2016-002732-32 IRST Protocol

Molecules. 2019 Feb 11;24(3):621. doi: 10.3390/molecules24030621.

Abstract

Radio-ligand therapy (RLT) with177Lu-PSMA-617 is a promising option for patients with metastatic castration-resistant prostate-cancer (mCRPC). A prospective phase-II study (EUDRACT/RSO,2016-002732-32) on mCRPC is ongoing at IRST (Meldola, Italy). A total of 9 patients (median age: 68 y, range: 53⁻85) were enrolled for dosimetry evaluation of parotid glands (PGs), kidneys, red marrow (RM) and whole body (WB). Folic polyglutamate tablets were orally administered as PGs protectors and 500 mL of a 10% mannitol solution was intravenously infused to reduce kidney uptake. The whole body planar image (WBI) and blood samples were acquired at different times post infusion (1 h, 16⁻24 h, 36⁻48 h and 120 h). Dose calculation was performed with MIRD formalism (OLINDA/EXM software). The median effective half-life was 33.0 h (range: 25.6⁻60.7) for PGs, 31.4 h (12.2⁻80.6) for kidneys, 8.2 h (2.5⁻14.7) for RM and 40.1 h (31.6⁻79.7) for WB. The median doses were 0.48 mGy/MBq (range: 0.33⁻2.63) for PGs, 0.70 mGy/MBq (0.26⁻1.07) for kidneys, 0.044 mGy/MBq (0.023⁻0.067) for RM and 0.04 mGy/MBq (0.02⁻0.11) for WB. A comparison with previously published dosimetric data was performed and a significant difference was found for PGs while no significant difference was observed for the kidneys. For PGs, the possibility of reducing uptake by administering glutamate tablets during RLT seems feasible while further research is warranted for a more focused evaluation of the reduction in kidney uptake.

Keywords: PSMA; dosimetry; protectors; theragnostic tracers.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Bone Marrow / chemistry
  • Dipeptides / administration & dosage*
  • Dipeptides / chemistry
  • Dipeptides / pharmacokinetics
  • Glutamic Acid / administration & dosage*
  • Glutamic Acid / therapeutic use
  • Half-Life
  • Heterocyclic Compounds, 1-Ring / administration & dosage*
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Heterocyclic Compounds, 1-Ring / pharmacokinetics
  • Humans
  • Infusions, Intravenous
  • Kidney / chemistry
  • Lutetium / administration & dosage*
  • Lutetium / pharmacokinetics
  • Male
  • Mannitol / administration & dosage*
  • Mannitol / therapeutic use
  • Middle Aged
  • Parotid Gland / chemistry
  • Prospective Studies
  • Prostate-Specific Antigen
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Radiation Dosage
  • Radioisotopes / administration & dosage*
  • Radioisotopes / pharmacokinetics
  • Radiopharmaceuticals / administration & dosage
  • Radiopharmaceuticals / pharmacokinetics
  • Tablets / administration & dosage

Substances

  • Dipeptides
  • Heterocyclic Compounds, 1-Ring
  • PSMA-617
  • Radioisotopes
  • Radiopharmaceuticals
  • Tablets
  • Glutamic Acid
  • Mannitol
  • Lutetium
  • Lutetium-177
  • Prostate-Specific Antigen