Radiobiological evaluation of the therapeutic effect of silver-111 for the ISOLPHARM project.

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Development
• Radiobiology

Background:

• The ISOLPHARM project aims to develop novel radiopharmaceuticals using radionuclides from the SPES facility.
• Silver-111 (Ag-111), a beta-emitting radiometal, is a promising candidate for Targeted Radionuclide Therapy (TRT).
• Preclinical research with Ag-111 is initiated using small quantities produced by the TRIGA Mark II nuclear reactor.

Purpose of the Study:

• To conduct the first radiobiological experiment using silver-111.
• To evaluate the effects of Ag-111 on cancer cell lines.
• To perform dosimetric analysis relating experimental outcomes to absorbed dose.

Main Methods:

• Administered varying concentrations of Ag-111 to UMR-106 rat osteosarcoma and LNCaP human prostate cancer cell lines.
• Assessed cell survival curves, DNA repair protein foci, and micronuclei formation.
• Performed dosimetric analysis using Monte Carlo simulations (Geant4) and MIRD formalism.

Main Results:

• Observed differential responses between the two cancer cell lines.
• Identified potential variations in DNA repair pathway thresholds influencing radiosensitivity.
• Highlighted limitations of the linear-quadratic model in this radiobiological context.

Conclusions:

• Silver-111 demonstrates differential cytotoxicity against cancer cell lines.
• Further dosimetric and radiobiological studies are warranted for Ag-111 TRT development.
• Cancer cell DNA repair mechanisms significantly influence Ag-111 efficacy.