Gold microspheres: a selective technique for producing biologically effective dose enhancement

Purpose: To investigate dose enhancement and radiosensitization associated with electrons produced and scattered from gold particles suspended in cell s in vitro and with tumour cells growing in vivo irradiated with low-energy photons. Materials and methods: CHO-KI, EMT-6 and DU-145 cells were irradiated with kilovoltage X-ray and Cs-137 beams in slowly stirred suspensions in the pre sence of various concentrations of gold particles (1.5-3.0 mu m); cell surv ival was measured by clonogenic assay. Gold particles were injected directl y into EMT-6 tumours growing in scid mice prior to their irradiation. Tumou r cell killing was assayed by an in vivo-in vitro technique. Results: Dose enhancement was confirmed by both Fricke dosimetry and cell k illing for 100, 140, 200 and 240 kVp X-rays, but not for Cs-137 gamma-rays. For the chemical dosimeter, a dose enhancement (DMF) of 1.42 was measured for 1% gold particle solutions irradiated with 200 kVp X-rays. When rodent and human cells were irradiated in the presence of 1% gold particles, DMF v alues at the 10% survival level ranged from 1.36 to 1.54, with an overall a verage value of 1.43. Preliminary attempts to deliver these gold particles to tumour cells in vivo by intra-tumour injection resulted in modest radios ensitization but extremely heterogeneous distribution. Conclusions: An increased biologically effective dose can be produced by go ld microspheres suspended in cell culture or distributed in tumour tissue e xposed to kilovoltage photon beams. With the increasing use of interstitial brachytherapy with isotopes that produce low-energy photons, high-Z partic les might find a role for significantly improving the therapeutic ratio.