Preparation, characterization and evaluation of [125I]-pirarubicin: A new therapeutic agent for urinary bladder cancer with potential for use as theranostic agent

Appl Radiat Isot. 2022 Jan:179:110007. doi: 10.1016/j.apradiso.2021.110007. Epub 2021 Oct 28.

Abstract

Improving urinary bladder cancer diagnosis, follow-up, and therapy tools to overcome existing limitations and increase survival rates is a highly desirable goal. In the current investigation, pirarubicin, a new generation antineoplastic anthracycline, was labeled with [125I] via an electrophilic substitution reaction. The reaction parameters were studied to optimize the iodination process. The labeled compound showed high radiochemical yield (98.5 ± 2.1%) and consistently remained above 90% for more than 20 h at room temperature and in the presence of serum at 37 °C. The binding of [125I]-pirarubicin to its target DNA-human topoisomerase II complex was assessed in-silico. The in-vitro tracer uptake by cancer cells was high and reached saturation (88.4 ± 2.3%) after 3 h with nuclei to cells ratio of 40 ± 1.2%. The labeled compound antiproliferative effect was much stronger than the unlabelled pirarubicin, as cleared by the growth inhibition test. Radiotoxicity improved cancer cells drug cytotoxicity. The in-vivo evaluation results showed that the [125I]-pirarubicin tends to preferentially accumulate in urinary bladder cancerous tissues.

Keywords: Diagnosis; Iodine-125; Molecular modeling; Pirarubicin; Treatment; Urinary bladder carcinoma.

MeSH terms

  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Humans
  • Iodine Radioisotopes / pharmacokinetics
  • Iodine Radioisotopes / therapeutic use*
  • Precision Medicine*
  • Urinary Bladder Neoplasms / radiotherapy*

Substances

  • Iodine Radioisotopes
  • Doxorubicin
  • pirarubicin
  • Iodine-125