Imaging assessment of photosensitizer emission induced by radionuclide-derived Cherenkov radiation using charge-coupled device optical imaging and long-pass filters.

BACKGROUND: Radionuclides produce Cherenkov radiation (CR), which can potentially activate photosensitizers (PSs) in phototherapy. Several groups have studied Cherenkov energy transfer to PSs using optical imaging; however, cost-effectively identifying whether PSs are excited by radionuclide-derived CR and detecting fluorescence emission from excited PSs remain a challenge. Many laboratories face the need for expensive dedicated equipment. AIM: To cost-effectively confirm whether PSs are excited by radionuclide-derived CR and distinguish fluorescence emission from excited PSs. METHODS: The absorbance and fluorescence spectra of PSs were measured using a microplate reader and fluorescence spectrometer to examine the photo-physical properties of PSs. To mitigate the need for expensive dedicated equipment and achieve the aim of the study, we developed a method that utilizes a charge-coupled device optical imaging system and appropriate long-pass filters of different wavelengths (manual sequential application of long-pass filters of 515, 580, 645, 700, 750, and 800 nm). Tetrakis (4-carboxyphenyl) porphyrin (TCPP) was utilized as a model PS. Different doses of copper-64 (64CuCl2) (4, 2, and 1 mCi) were used as CR-producing radionuclides. Imaging and data acquisition were performed 0.5 h after sample preparation. Differential image analysis was conducted by using ImageJ software (National Institutes of Health) to visually evaluate TCPP fluorescence. RESULTS: The maximum absorbance of TCPP was at 390-430 nm, and the emission peak was at 670 nm. The CR and CR-induced TCPP emissions were observed using the optical imaging system and the high-transmittance long-pass filters described above. The emission spectra of TCPP with a peak in the 645-700 nm window were obtained by calculation and subtraction based on the serial signal intensity (total flux) difference between 64CuCl2 + TCPP and 64CuCl2. Moreover, the differential fluorescence images of TCPP were obtained by subtracting the 64CuCl2 image from the 64CuCl2 + TCPP image. The experimental results considering different 64CuCl2 doses showed a dose-dependent trend. These results demonstrate that a bioluminescence imaging device coupled with different long-pass filters and subtraction image processing can confirm the emission spectra and differential fluorescence images of CR-induced TCPP. CONCLUSION: This simple method identifies the PS fluorescence emission generated by radionuclide-derived CR and can contribute to accelerating the development of Cherenkov energy transfer imaging and the discovery of new PSs.

Response of personal dosemeters on various age-specific anthropometric phantoms under external irradiation applied to areas affected by the 2011 Fukushima Daiichi nuclear accident.

We experimentally obtained the responses of two personal dosemeters (PDs, D-shuttle and Dose-i) attached on five age-specific phantoms under rotational irradiation geometry, which simulated an environment that was radiologically affected by the 2011 Fukushima nuclear accident using of a 137Cs source. Although the PD responses showed an angular phase shift by the PD position on the phantoms, the angular dependence was small when the contamination was widely distributed. The PD responses decreased as much as ~10% with the increase in the phantoms' body size. Although there were ~17% variations in the PD/ADE (ambient dose equivalent) ratio depending on the different PDs, this variation was due to the fact that D-shuttle was calibrated with the inclusion of a safety margin. The PD/ADE ratios were similar to the effective dose to ADE ratios for corresponding age-specific phantoms. Our results suggest that these two PDs can provide reasonable estimates for age-dependent effective doses.

Radiotheranostic Agent 64Cu-cyclam-RAFT-c(-RGDfK-)4 for Management of Peritoneal Metastasis in Ovarian Cancer.

PURPOSE: Ovarian cancer peritoneal metastases (OCPMs) are a pathophysiologically heterogeneous group of tumors that are rarely curable. αVß3 integrin (αVß3) is overexpressed on tumoral neovessels and frequently on ovarian cancer cells. Here, using two clinically relevant αVß3-positive OCPM mouse models, we studied the theranostic potential of an αVß3-specific radiopeptide, 64Cu-cyclam-RAFT-c(-RGDfK-)4 (64Cu-RaftRGD), and its intra- and intertumoral distribution in relation to the tumor microenvironment. EXPERIMENTAL DESIGN: αVß3-expressing peritoneal and subcutaneous models of ovarian carcinoma (IGR-OV1 and NIH:OVCAR-3) were established in nude mice. 64Cu-RaftRGD was administered either intravenously or intraperitoneally. We performed intratumoral distribution (ITD) studies, PET/CT imaging and quantification, biodistribution assay and radiation dosimetry, and therapeutic efficacy and toxicity studies. RESULTS: Intraperitoneal administration was an efficient route for targeting 64Cu-RaftRGD to OCPMs with excellent tumor penetration. Using the fluorescence surrogate, Cy5.5-RaftRGD, in our unique high-resolution multifluorescence analysis, we found that the ITD of 64Cu-RaftRGD was spatially distinct from, but complementary to, that of hypoxia. 64Cu-RaftRGD-based PET enabled clear visualization of multiple OCPM deposits and ascites and biodistribution analysis demonstrated an inverse correlation between tumor uptake and tumor size (1.2-17.2 mm). 64Cu-RaftRGD at a radiotherapeutic dose (148 MBq/0.357 nmol) showed antitumor activities by inhibiting tumor cell proliferation and inducing apoptosis, with negligible toxicity. CONCLUSIONS: Collectively, these results demonstrate the all-in-one potential of 64Cu-RaftRGD for imaging guided radiotherapy of OCPM by targeting both tumoral neovessels and cancerous cells. On the basis of the ITD finding, we propose that pairing αVß3- and hypoxia-targeted radiotherapies could improve therapeutic efficacy by overcoming the heterogeneity of ITD encountered with single-agent treatments.

Correlation analysis of organ doses determined by Monte Carlo simulation with dose metrics for patients undergoing chest-abdomen-pelvis CT examinations.

OBJECTIVES: This study aimed to determine organ doses based on Monte Carlo (MC) simulations for individual patients undergoing routine adult chest abdomen-pelvis computed tomography (CT) examinations and to evaluate the correlations of organ doses with patient size and dose metrics. METHODS: MC simulations were performed by reading detailed descriptions of the CT scanner, scanning parameters, and CT images of phantoms and patients into the simulation software. The simulation models were validated by comparing the simulated doses with the doses measured by in-phantom dosimetry using radiophotoluminescent glass dosimeters and an adult anthropomorphic phantom, and organ doses for 80 patients were determined from the simulation results. To obtain patient size and dose metrics, body mass index and volume computed tomography dose index (CTDIvol) data were collected. Water equivalent diameter (WED) was calculated from the CT images of each patient. Size-specific dose estimates (SSDE) were calculated using CTDIvol and average WED over the scan range, and organ specific SSDE were calculated using the average CTDIvol and WED over each organ position. The correlations of organ doses with dose metrics were evaluated using coefficients of determination. RESULTS: Organ doses increased with patient size, and the doses for obese were approximately two to three times higher than those for underweight patients. Organ doses exhibited stronger linear relationships with organ specific SSDE (R2 ≥ 0.82) than other dose metrics. CONCLUSIONS: The linear regression fits between organ doses determined by MC simulation and organ-specific SSDE are valuable for simplified and accurate organ dose estimation for individual patients undergoing CT examinations.

Estimation of organ doses and effective doses in image-guided respiration-gated radiotherapy.

Dose conformity in thoracic and abdominal ion-beam radiotherapy is degraded by respiratory motion. To improve conformity, an image-guided respiration-gated system can be used in the treatment room. The purpose of this study was to estimate the organ doses and effective doses to patients from an image-guided respiration-gated system. Glass dosemeters were inserted into an adult anthropomorphic phantom and were attached to the surface on the phantom. The phantom was placed on the treatment couch, and the imaging dose from fluoroscopy was evaluated. In addition to the organ doses, the effective doses were also estimated according to the ICRP Publication 103. The irradiation time is over 3-5 min per beam angle. When image acquisition conditions were assumed for thoracic treatment, the effective doses and maximal skin doses were 0.48-0.79 mSv and 5.9-9.9 mGy, respectively. The estimated doses can be the base data for considering radiological protection in the radiotherapy.

Estimation of absorbed radiation dose rates in wild rodents inhabiting a site severely contaminated by the Fukushima Dai-ichi nuclear power plant accident.

The dose rates of radiation absorbed by wild rodents inhabiting a site severely contaminated by the Fukushima Dai-ichi Nuclear Power Plant accident were estimated. The large Japanese field mouse (Apodemus speciosus), also called the wood mouse, was the major rodent species captured in the sampling area, although other species of rodents, such as small field mice (Apodemus argenteus) and Japanese grass voles (Microtus montebelli), were also collected. The external exposure of rodents calculated from the activity concentrations of radiocesium ((134)Cs and (137)Cs) in litter and soil samples using the ERICA (Environmental Risk from Ionizing Contaminants: Assessment and Management) tool under the assumption that radionuclides existed as the infinite plane isotropic source was almost the same as those measured directly with glass dosimeters embedded in rodent abdomens. Our findings suggest that the ERICA tool is useful for estimating external dose rates to small animals inhabiting forest floors; however, the estimated dose rates showed large standard deviations. This could be an indication of the inhomogeneous distribution of radionuclides in the sampled litter and soil. There was a 50-fold difference between minimum and maximum whole-body activity concentrations measured in rodents at the time of capture. The radionuclides retained in rodents after capture decreased exponentially over time. Regression equations indicated that the biological half-life of radiocesium after capture was 3.31 d. At the time of capture, the lowest activity concentration was measured in the lung and was approximately half of the highest concentration measured in the mixture of muscle and bone. The average internal absorbed dose rate was markedly smaller than the average external dose rate (<10% of the total absorbed dose rate). The average total absorbed dose rate to wild rodents inhabiting the sampling area was estimated to be approximately 52 µGy h(-1) (1.2 mGy d(-1)), even 3 years after the accident. This dose rate exceeds 0.1-1 mGy d(-1) derived consideration reference level for Reference rat proposed by the International Commission on Radiological Protection (ICRP).

Comparison of neutron fluxes in an 18-MeV unshielded cyclotron room and a 16.5-MeV self-shielded cyclotron room.

Some medical compact cyclotrons have self-shielding to reduce neutron fluxes. Thermal neutron fluxes in an 18-MeV unshielded cyclotron room and in a 16.5-MeV self-shielded cyclotron room were evaluated. In addition, the radioactivities in concrete and metals due to thermal neutrons in the cyclotron rooms for 30 years were calculated of operation such that the sum of the ratio of the nuclide concentration to the nuclide clearance level was equal to 1. The thermal neutron flux from the unshielded cyclotron was approximately 10(2) cm(-2) s(-1), whereas that from the self-shielded cyclotron was approximately 10(2) cm(-2) s(-1). The thermal neutron fluxes for concrete, stainless steel, vessel steel, and aluminum that reached their clearance levels were 9.80 × 10(4), 2.17 × 10(3), 1.87 × 10(4), and 2.41 × 10(5) cm(-2) s(-1), respectively. The specific activities in the cyclotron room were found to be sufficiently below the clearance level when the self-shield was employed.

Radiologic assessment of a self-shield with boron-containing water for a compact medical cyclotron.

The cyclotron at our hospital has a self-shield of boron-containing water. The amount of induced radioactivity in the boron-containing water shield of a compact medical cyclotron has not yet been reported. In this study, we measured the photon and neutron dose rates outside the self-shield during cyclotron operation. We estimated the induced radioactivities of the boron-containing water used for the self-shield and then measured them. We estimated the activation of concrete outside the self-shield in the cyclotron laboratory. The thermal neutron flux during cyclotron operation was estimated to be 4.72 × 10(2) cm(-2) s(-1), and the activation of concrete in a cyclotron laboratory was about three orders of magnitude lower than the clearance level of RS-G-1.7 (IAEA). The activity concentration of the boron-containing water did not exceed the concentration limit for radioactive isotopes in drainage in Japan and the exemption level for Basic Safety Standards. Consequently, the boron-containing water is treatable as non-radioactive waste. Neutrons were effectively shielded by the self-shield during cyclotron operation.

Induced radioactive nuclides of 10-MeV radiotherapy accelerators detected by using a portable HP-Ge survey meter.

The radioactivation of linear accelerator components for radiation therapy is interest for radiation protection in general, and particularly, when decommissioning these structures. The energy spectra of gamma rays emitted from the heads of two accelerator models, EXL-15SP and Clinac iX, after 10-MeV X-ray irradiation, were measured using a high-purity germanium semiconductor survey meter. After spectrum analyses, activities of (24)Na, (28)Al, (54)Mn, (56)Mn, (57)Ni, (58)Co, (60)Co, (64)Cu, (65)Zn, (122)Sb, (124)Sb, (181)W, (187)W, (196)Au, and (198)Au were detected. One centimetre deep dose-equivalent rate of the heads of the linear accelerator was measured using the survey meter. The dose rate decreased to ∼10 % of its initial rate after 1 week. Long-term activations were few, the radioactivity level was low, and a cooling time of several days was effective for reducing dose rate to an acceptable level for decommissioning.

Photoexcitation of K-shell and L-shell hollow beryllium.

We have observed K-shell and L-shell hollow beryllium atoms (2s(2)2p3s and 1s3s(2)3p) created by photoexcitation using synchrotron radiation. Resonance shapes were fitted to the Fano profile and the parameters were deduced. A Dirac-Fock calculation was performed to identify the configuration of the peaks and to predict other hollow atomic peaks. The results of the calculation were in good agreement with the experimental data. The comparison of the transition strength has revealed that the three-electron photoexcitation to the 1s3s(2)3p configuration is stronger than the two-electron photoexcitation to the 2s(2)2p3s configuration. This is attributed to the large overlap between the 2s orbital of the ground state (1s(2)2s(2)) with the orbital of the L-shell hollow state (1s3s(2)3p).

Double photoexcitation of helium in a strong dc electric field.

We report the first experimental measurements of the effect of an applied field on the photoexcitation and autoionization of doubly excited states of helium. Ground-state photoionization spectra have been measured in the region below the He+(N=2) threshold with static electric fields of up to 84.4 kV/cm across the interaction region. The results are compared to the theoretical calculations of Chung et al. [J. Phys. B 34, 165 (2001)]], which are the only calculations available in this regime. Transitions to several states in the N=2, n=6 manifold are assigned, and a wealth of new structure is observed. Our data show that many more series are mixed in by the field than those predicted by theory.