In vitro and in vivo response of PSMA-617 radiolabeled with CA and NCA lutetium-177

Appl Radiat Isot. 2022 Feb:180:110064. doi: 10.1016/j.apradiso.2021.110064. Epub 2021 Dec 14.

Abstract

The PSMA-targeted radionuclide therapy has been explored since 2015 with radioisotope lutetium-177, whose β- emission range is adequate for micrometastases treatment. This radioisotope is obtained by two different production routes that directly affect the specific activity of lutetium-177 (non-carrier added and carrier added) and, consequently, the specific activity of radiopharmaceuticals, like 177Lu-PSMA-617. The influence of the specific activity of lutetium-177 on the properties of the radiopharmaceutical PSMA-617 was evaluated through pre-clinical studies. The in vitro study pointed to a lower constant of dissociation with non-carrier added lutetium-177 due to the difference in the specific activity. However, competition and internalization assays resulted in similar results for both lutetium-177. Based on these pre-clinical experiments, the total in vitro tumor cell binding and tumor uptake in vivo were similar, with no influence of the specific activity of the 177Lu-PSMA-617. Regardless the specific activity did not directly affect tumor uptake, the tumor/non-target organs ratios were higher for the radiopharmaceutical labeled with carrier added lutetium-177, which had the lowest specific activity.

Keywords: Lutetium-177; PSMA-617; Specific activity.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Dipeptides / pharmacology*
  • Heterocyclic Compounds, 1-Ring / pharmacology*
  • Humans
  • Lutetium / chemistry*
  • Male
  • Mice
  • Mice, SCID
  • Prostate-Specific Antigen / pharmacology*
  • Prostatic Neoplasms / drug therapy*
  • Radioisotopes / chemistry*
  • Radiopharmaceuticals / chemistry*
  • Radiopharmaceuticals / pharmacology*
  • Tissue Distribution
  • Xenograft Model Antitumor Assays

Substances

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