Effect of magnetite nanoparticle agglomerates on the destruction of tumor spheroids using high intensity focused ultrasound.

Magnetite (Fe(3)O(4)) nanoparticle agglomerates have been shown to enhance the degree of inertial cavitation induced by high-intensity focused ultrasound (HIFU). To investigate the effect of these particles on the destruction of tumor spheroids using HIFU, HeLa spheroids were insonated in the presence and absence of magnetite nanoparticle agglomerates. The HIFU transducer was operated with a frequency of 1.1 MHz, pulse repetition frequency of 1.67 kHz, 5% and 50% duty cycles and peak negative focal pressure of 7.2 MPa for 10 s. The significant increase in the HIFU-induced inertial cavitation caused by the presence of magnetite particles at 50% duty cycle was sufficient to cause cell lysis and disintegrate the whole spheroid (p ≤ 0.001). This suggests that magnetite nanoparticle agglomerates can enhance the efficacy of HIFU in tumor ablation and other related therapies.

Feasibility study of quantitative radioactivity monitoring of tumor tissues inoculated into mice with a planar positron imaging system (PPIS).

OBJECTIVE: The objective of this study was to evaluate whether the radioactivity of tumor tissues inoculated into mice can be monitored quantitatively with a planar positron imaging system (PPIS). METHODS: (18)F-fluoro-D-glucose, (18)F-fluorothymidine, or D-(18)F-fluoromethyl tyrosine were intravenously administered into HeLa-bearing mice. In vivo uptake of each labeled compound in tumors was monitored with the PPIS, followed by the measurement of radioactivity in tumor tissue using tissue dissection analysis. The standardized uptake values (SUVs) in PPIS measurement and ex vivo tissue dissection analysis were derived using the tumor volume and tumor weight, respectively. RESULTS: Radioactivities of tumors in mice obtained via PPIS imaging correlated significantly with those by tissue dissection analysis. The SUV derived by the PPIS data and the estimated tumor volume correlated roughly with those by ex vivo tissue dissection analysis. CONCLUSIONS: The results of our experiment indicate the feasibility of noninvasive, quantitative tumor monitoring in mouse/rat studies with the PPIS.

Ultrasonically induced alterations of cultured tumour cells.

OBJECTIVE: The aim of this study was to establish: (i) which phase of the cell cycle is most sensitive to ultrasonic action; and (ii) whether and in which way ultrasound can influence components of the cytoskeleton. METHODS: HeLa cell monolayers grown on glass cover-slips in DEM medium were used in all experiments. For proliferation studies, the cell monolayers were trypsinized and the cells were resuspended in fresh medium. The structure of the cytoskeleton was studied by means of the indirect immunofluorescence method. The cells were sonicated by a cw ultrasound of 0.8 MHz at low SA intensities (50, 100 and 500 mW/cm2) for 5 and 10 min. RESULTS: The analysis of proliferation demonstrated that cells were most sensitive when undergoing M- and S-phases of the cell cycle. The ultrasonically induced disassembly of cytoskeleton components was most marked in microtubules and microfilaments due to depolymerization of basic proteins (tubulin and actin). The reaction of intermediate filaments was distinctly weaker. CONCLUSIONS: In-vitro treatment of tumour cells with low intensity ultrasound results in partial inhibition of proliferation as well as in partial disassembly of all components of the cytoskeleton. Ultrasonically induced changes of the cytoskeleton seem to be non-specific and temporary.

Ultrasound enhances gene expression of liposomal transfection.

RATIONALE AND OBJECTIVES: Cationic liposomes are under development as delivery agents for gene therapy. The authors studied the effect of ultrasound on gene expression in cell cultures during liposomal transfection experiments. METHODS: Cationic liposomes of dipalmitoylethylphosphocholine and dioleoylphosphatidylethanolamine were used to transfect cultured HeLa, NIH/3T3, and C127I cells with the chloramphenicol acetyl transferase (CAT) gene. A cell viability assay was performed on cultured HeLa cells that were exposed to varying durations (5 seconds or 30 seconds) and intensities of 1 MHz continuous-wave therapeutic ultrasound after transfection, and gene expression was measured 48 hours later. RESULTS: Cells survived 30 seconds or less at a power level of 0.5 watts/cm2 but died when exposed for 60 seconds or longer. Exposures of 5 seconds and 30 seconds of ultrasound resulted in significant increases in gene expression in all three cell types tested in this experiment. CONCLUSIONS: Relatively low levels of ultrasound energy can be used to enhance gene expression from liposomal transfection. Additional experiments are needed to optimize this process and clarify the mechanisms involved.