ABSTRACT
PURPOSE: The efficacy of a boron-containing cholesteryl ester compound (BCH) as a boron neutron capture therapy (BNCT) agent for the targeted irradiation of PC-3 human prostate cancer cells was examined. MATERIALS AND METHODS: Liposome-based delivery of BCH was quantified with inductively coupled plasma-mass spectrometry (ICP-MS) and high-performance liquid chromatography (HPLC). Cytotoxicity of the BCH-containing liposomes was evaluated with neutral red, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), and lactate dehydrogenase assays. Colony formation assays were utilized to evaluate the decrease in cell survival due to high-linear energy transfer (LET) particles resulting from (10)B thermal neutron capture. RESULTS: BCH delivery by means of encapsulation in a lipid bilayer resulted in a boron uptake of 35.2 ± 4.3 µg/10(9) cells, with minimal cytotoxic effects. PC-3 cells treated with BCH and exposed to a 9.4 × 10(11) n/cm(2) thermal neutron fluence yielded a 20-25% decrease in clonogenic capacity. The decreased survival is attributed to the generation of high-LET α particles and (7)Li nuclei that deposit energy in densely ionizing radiation tracks. CONCLUSION: Liposome-based delivery of BCH is capable of introducing sufficient boron to PC-3 cells for BNCT. High-LET α particles and (7)Li nuclei generated from (10)B thermal neutron capture significantly decrease colony formation ability in the targeted PC-3 cells.
Subject(s)
Boron Neutron Capture Therapy/methods , Prostatic Neoplasms/radiotherapy , Boron/administration & dosage , Cell Line, Tumor , Cell Survival/radiation effects , Cholesterol Esters/administration & dosage , Drug Delivery Systems , Humans , Isotopes/administration & dosage , Linear Energy Transfer , Liposomes , Male , Prostatic Neoplasms/pathologyABSTRACT
The new nanodosimetry-based linear-quadratic (LQ) formula has been reviewed for mixed-LET irradiation. V-79 Chinese hamster cells have been irradiated with a mixed-LET field of fission neutrons and gamma rays at the University of Maryland Training Reactor (MUTR). The results show that the experimental survival curve agrees well with that predicted by the new nanodosimetry-based LQ model. The experimental study described in this note, therefore, serves as a validation for the new model to be used for mixed-LET radiotherapies, e.g. 252Cf brachytherapy.