First radiotherapy of human metastatic brain tumors delivered by a computerized tomography scanner (CTRx)

Rose, J.; Norman, Amos; Ingram, Marylou; Aoki, Chuck T.; Solberg, Timothy D.; Mesa, Albert

doi:10.1016/s0360-3016(99)00347-8

Cited by 85 publications

(72 citation statements)

References 12 publications

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“…Santos Mello [54] achieved an intratumoural concentration of 5 mg ml -1 iodine and demonstrated reduced tumour growth delay in a rabbit model. These results led to a Phase I feasibility trial in which 8 patients received 3-5 weekly 5-Gy boosts with 140-kVp X-rays to intracranial metastases while undergoing whole brain radiotherapy with 40 Gy in 20 fractions over 4 weeks with 6-MV photons [55]. IV iodine contrast medium was administered prior to radiation and 140-kVp X-rays were delivered in 360 o rotations in three planes to minimise skull dose.…”

Section: Gold Nanoparticles As Radiosensitisersmentioning

confidence: 99%

Gold nanoparticles as novel agents for cancer therapy

Jain¹,

Hirst²,

O’Sullivan³

2012

BJR

904

568

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ABSTRACT. Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. This review introduces the field of nanotechnology with a focus on recent gold nanoparticle research which has led to early-phase clinical trials. In particular, the pre-clinical evidence for gold nanoparticles as sensitisers with ionising radiation in vitro and in vivo at kilovoltage and megavoltage energies is discussed.

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Section: Gold Nanoparticles As Radiosensitisersmentioning

confidence: 99%

Gold nanoparticles as novel agents for cancer therapy

Jain¹,

Hirst²,

O’Sullivan³

2012

BJR

904

568

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“…The aim of the technique is to obtain sharp isodoses around the tumour, using both the photoelectric effect on the high-Z element present in the tumour and the circular irradiation ballistic . Phase I clinical trial was published for treatment of patients with metastatic brain tumours, loaded with iodinated contrast agents, and demonstrated the feasibility of this technique (Rose et al, 1999). The dose-enhancement effect is hence theoretically optimised with 140 kV p X-rays beams when compared with 10 MV, and, interestingly enough even in cases of stereotactic irradiation.…”

Section: Iodine Contrast Agent As Radiation Sensitisermentioning

confidence: 99%

“…Ionised heavy atoms then reorganise and emit low-energy Auger electrons cascades, able to damage DNA because of their nuclear localisation. In a less specific way, Norman et al developed another approach: the use of a conventional kilovoltage scanner to treat iodine-loaded tumours (Iwamoto et al, 1990;Rose et al, 1999). By increasing the tumour density and focussing a kilovoltage beam on it, interaction cross-sections are improved in the tumour only, due to the photoelectric effect, and the dose distribution is concentrated inside the tumour (Solberg et al, 1992a(Solberg et al, , 1995Mesa et al, 1999).…”

mentioning

confidence: 99%

Synchrotron radiation-based experimental determination of the optimal energy for cell radiotoxicity enhancement following photoelectric effect on stable iodinated compounds

et al. 2004

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This study was designed to experimentally evaluate the optimal X-ray energy for increasing the radiation energy absorbed in tumours loaded with iodinated compounds, using the photoelectric effect. SQ20B human cells were irradiated with synchrotron monochromatic beam tuned at 32.8, 33.5, 50 and 70 keV. Two cell treatments were compared to the control: cells suspended in 10 mg ml À1 of iodine radiological contrast agent or cells pre-exposed with 10 mM of iodo-desoxyuridine (IUdR) for 48 h. Our radiobiological end point was clonogenic cell survival. Cells irradiated with both iodine compounds exhibited a radiation sensitisation enhancement. Moreover, it was energy dependent, with a maximum at 50 keV. At this energy, the sensitisation calculated at 10% survival was equal to 2.03 for cells suspended in iodinated contrast agent and 2.60 for IUdR. Cells pretreated with IUdR had higher sensitisation factors over the energy range than for those suspended in iodine contrast agent. Also, their survival curves presented no shoulder, suggesting complex lethal damages from Auger electrons. Our results confirm the existence of the 50 keV energy optimum for a binary therapeutic irradiation based on the presence of stable iodine in tumours and an external irradiation. Monochromatic synchrotron radiotherapy concept is hence proposed for increasing the differential effect between healthy and cancerous tissue irradiation.

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“…Another promising technique, computed tomography therapy, uses a modified X-ray scanner to irradiate brain tumors loaded with iodinated contrast agent. This technique was shown to result in a supra-additive response, perhaps because of an increased photoelectric effect (5)(6)(7)(8). A monochromatic radiation beam would potentially enhance this physical effect.…”

Section: Introductionmentioning

confidence: 99%

Cure of Fisher Rats Bearing Radioresistant F98 Glioma Treated with cis -Platinum and Irradiated with Monochromatic Synchrotron X-Rays

et al. 2004

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High-grade gliomas are usually of poor prognosis, and conventional radiotherapy, even combined with chemotherapy, still fails to improve the survival of patients. Here, we propose an innovative therapeutic approach combining synchrotron radiation with cis-diamminedichloroplatinum (II) (CDDP). As suggested previously, monochromatic synchrotron irradiation of CDDP at 78.8 keV, just above the 78.4 keV platinum absorption K-edge, leads to an enhanced photoelectric effect and an increased local toxicity. To select a particular radiation energy that could provide supraadditive effect, we used pulsed-field gel electrophoresis to assess yields of DNA double-strand breaks induced in rat F98 glioma cells after CDDP treatment combined with synchrotron X-rays. Thereafter, intracerebral CDDP injection combined with synchrotron X-rays was applied to Fisher rats bearing F98 glioma. CDDP concentrations were mapped by synchrotron X-ray microfluorescence. An extra number of more slowly repaired double strand breaks were observed when irradiating CDDP-treated F98 cells at 78.8 keV. In vivo treatments were then performed with different radiation doses and CDDP concentrations. All cell inoculations in rat brain resulted in tumor development, and tumor presence was controlled by computed tomography. Among all of the conditions tested, the combination of 3 g of CDDP with 15 Gy resulted in the largest median survival time (206 days). After 1 year, about 34% of treated rats were still alive. This preclinical finding, validated by molecular analysis, represents the most protracted survival reported with this radioresistant glioma model and demonstrates the interest in powerful monochromatic X-ray sources as new tools for cancer treatments.

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First radiotherapy of human metastatic brain tumors delivered by a computerized tomography scanner (CTRx)

Cited by 85 publications

References 12 publications

Gold nanoparticles as novel agents for cancer therapy

Gold nanoparticles as novel agents for cancer therapy

Synchrotron radiation-based experimental determination of the optimal energy for cell radiotoxicity enhancement following photoelectric effect on stable iodinated compounds

Cure of Fisher Rats Bearing Radioresistant F98 Glioma Treated with cis -Platinum and Irradiated with Monochromatic Synchrotron X-Rays

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