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

INTRODUCTION: The ISOLPHARM project has the aim of developing novel radiopharmaceuticals using the wide choice of radionuclides produced by Isotope Separation OnLine (ISOL) at LNL-INFN in the SPES facility, which is currently nearing completion. One of the most promising candidates for Targeted Radionuclide Therapy (TRT) is the beta-emitting radiometal silver-111, obtainable carrier-free irradiating a uranium carbide target with a proton beam and applying the ISOL technique. Until SPES will become fully operational, small quantities of silver-111 are produced by the TRIGA Mark II nuclear reactor hosted by the LENA facility of the University of Pavia to begin the preclinical research. The present work concerns the first radiobiological experiment involving silver-111. METHODS: Different activity concentrations of the aforementioned radiometal are administered to the UMR-106 rat osteosarcoma and LNCaP human prostate cancer cell lines through the culture medium. The survival curves after four and six days of exposure, as well as the recurrence of foci of DNA repair proteins and micronuclei, are evaluated as a function of the absorbed dose and compared to the control cultures. According to the MIRD formalism, a dosimetric analysis is performed taking advantage of cellular S-values simulated with the Monte Carlo code Geant4 in a generalized cell geometry. This makes it possible to relate the experimental outcome, namely the surviving cells after the exposure cycles, to the absorbed dose in the cell nucleus or in the whole cell environment. RESULTS AND DISCUSSION: The results show a difference in the response of the two cell lines, probably due to the thresholds of their DNA repair pathways, and highlight a possible weakness of the linear-quadratic model when applied to this kind of radiobiological studies.