Carbon ion radiotherapy (C-ion RT) offers superior dose conformity in the treatment of deep-seated tumors compared with conventional X-ray therapy. In addition, carbon ion beams have a higher relative biological effectiveness compared with protons or X-ray beams. C-ion RT for the first patient at Gunma University Heavy Ion Medical Center (GHMC) was initiated in March of 2010. The major specifications of the facility were determined based on the experience of clinical treatments at the National Institute of Radiological Sciences (NIRS), with the size and cost being reduced to one-third of those at NIRS. The currently indicated sites of cancer treatment at GHMC are lung, prostate, head and neck, liver, rectum, bone and soft tissue. Between March 2010 and July 2011, a total of 177 patients were treated at GHMC although a total of 100 patients was the design specification during the period in considering the optimal machine performance. In the present article, we introduce the facility set-up of GHMC, including the facility design, treatment planning systems, and clinical preparations.

The efficacy and toxicity of five-fraction CyberKnife radiotherapy were evaluated in patients with large brain metastases in critical areas. A total of 85 metastases in 78 patients, including tumors >30 cm3 (4 cm in diameter) were treated with five-fraction CyberKnife radiotherapy with a median marginal dose of 31 Gy at a median prescribed isodose of 58%. Changes in the neurological manifestations, local tumor control, and adverse effects were investigated after treatment. The surrounding brain volumes circumscribed with 28.8 Gy (single dose equivalent to 14 Gy: V14) were measured to evaluate the risk of radiation necrosis. Neurological manifestations, such as motor weakness, visual disturbances and aphasia improved in 28 of 55 patients (50.9%). Local tumor control was obtained in 79 of 85 metastases (92.9%) during a median follow-up of eight months. Symptomatic edema occurred in 10 patients, and two of them (2.6%) required surgical resection because of radiation necrosis. The V14 of these patients was 3.0–19.7 cm3. There were 16 lesions with a V14 of ≥7.0 cm3, and two of these lesions developed extensive brain edema due to radiation necrosis. None of the patients with a V14 of <7.0 cm3 exhibited edema requiring surgical intervention. We therefore conclude that a high rate of local tumor control and low rates of complications can be obtained after five-fraction CyberKnife radiotherapy for large metastases in critical areas. The V14 of the surrounding brain is therefore a useful indicator for the risk of radiation necrosis in patients with large metastases.

The efficacy and toxicity of three-fraction CyberKnife radiotherapy were evaluated in patients with brain metastases in critical areas. One hundred and fifty-nine metastases in 145 patients including tumors >10 cm3 were treated with three-fraction CyberKnife radiotherapy with a median marginal dose of 27 Gy at a median prescribed isodose of 60%. Changes in the neurological manifestations, local tumor control and adverse effects were investigated after treatment. The surrounding brain volumes circumscribed with 23.1 Gy (single dose equivalence of 14 Gy: V14) were measured to evaluate the risk of adverse effects. Neurological manifestations, such as motor weakness, visual disturbances and aphasia improved in 26 of 97 patients (26.8%). Local tumor control was obtained in 137 of 143 metastases (95.8%) during a median follow-up of 7 months. Nine patients had symptomatic edema and three of them (2.1%) required surgical resection because of radiation necrosis. The V14 of these patients was 4.6–31.5 cm3. There were 35 lesions with a V14 of 7 cm3 or more and three of them developed extensive brain edema due to radiation necrosis. None of the patients with a V14 of <7 cm3 exhibited edema requiring an operation. We therefore conclude that a high rate of local tumor control and low rates of complications are obtained after three-fraction CyberKnife radiotherapy for metastases in critical areas. The V14 of the surrounding brain therefore seems to be a useful indicator for the risk evaluation of radiation necrosis in patients with larger metastases.

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We report here the ribosomal synthesis of methyllanthionine-containing cyclic peptides involving a site-specific incorporation of vinylglycine under the reprogrammed genetic code, followed by the isomerization of the vinylglycine to dehydrobutyrine, and the subsequent intramolecular Michael addition of a cysteine residue placed at a downstream position of the vinylglycine.

We have been developing a medical imaging technique using a Compton camera. This study evaluates the feasibility of clear imaging with Tc andF simultaneously, and demonstrates in vivo imaging with Tc and/orF. We used a Compton camera with silicon and cadmium telluride (Si/CdTe) semiconductors. We estimated the imaging performance of the Compton camera for 141 keV and 511 keV gamma rays from Tc andNa, respectively. Next, we simultaneously imaged Tc andF point sources to evaluate the cross-talk artifacts produced by a higher energy gamma-ray background. Then, in the in vivo experiments, three rats were injected with Tc-dimercaptosuccinic acid and/orF-fluorodeoxyglucose and imaged. The Compton images were compared with PET images. The rats were euthanized, and the activities in their organs were measured using a well counter. The energy resolution and spatial resolution were measured for the sources. No apparent cross-talk artifacts were observed in the practical-activity ratio (Tc:F  =  1:16). We succeeded in imaging the distributions of Tc andF simultaneously, and the results were consistent with the PET images and well counter measurements. Our Si/CdTe Compton camera can thus work as a multi-tracer imager, covering various SPECT and PET probes, with less cross-talk artifacts in comparison to the conventional Anger cameras using a collimator. Our findings suggest the possibility of human trials.

We describe a new method for estimating the beam range in heavy-ion radiation therapy by measuring the ion beam bremsstrahlung. We experimentally confirm that the secondary electron bremsstrahlung process provides the dominant bremsstrahlung contribution. A Monte Carlo simulation shows that the number of background photons from annihilation gamma rays is about 1% of the bremsstrahlung strength in the low-energy region used in our estimation (63-68 keV). Agreement between the experimental results and the theoretical prediction for the characteristic shape of the bremsstrahlung spectrum validates the effectiveness of our new method in estimating the ion beam range.

Spread-out Bragg peaks made by ridge filters or wheel range modulators are used in charged particle therapy with passive methods to achieve uniform biological responses in irradiated tumors. Following the biological responses needed to design the ridge filters, which were developed at the National Institute of Radiological Sciences in Japan, new ridge filters were designed using recent developments in heavy-ion reactions and dosimetry. The Monte Carlo code of Geant4 was used to calculate the qualities of carbon ion beams in a water phantom. The results obtained from the simulation were corrected so that they agreed with the measurements of depth dose distributions. The calculations of biological responses to fragments other than carbon ions were assumed to be for helium ions. The measured dose distributions with the designed ridge filters were compared to the calculated distributions. A beam modifying system using this adaptable method was successively applied to carbon ion therapy at Gunma University.