Search Results (14)

In oncology, tremendous research has been conducted on the use of alternative minimally invasive techniques for cancer treatment and diagnosis. The use of biophotonic techniques as a standalone treatment or together with conventional imaging techniques has gained interest among researchers in recent years, while biophotonic therapies such as photothermal and photodynamic therapies tend to bring the use of non-ionizing radiation in therapy back into the spotlight due to the progressive development of optical instrumentation, enhancement agents, molecular probes, light sources and nanocarriers. Thus, the coupling of non-ionizing with ionizing radiation (IR) and the combination of nanomedicine with nuclear medicine procedures are considered to be revolutionary strategies to optimize the therapeutic efficacy of biophotonic modalities and to develop theranostic applications for the better diagnosis and treatment of cancer. Recently, the low-intensity Cerenkov light emitted by tissues as a byproduct of the IR–biostructure interaction has been suggested as an effective internal light source that can trigger phototherapy and guide radiotherapy dosimetry using Cerenkov imaging. This review also provides an overview of in vitro and in vivo studies regarding the use of Cerenkov radiation produced by X-rays or radionucleotides and combined with nanoparticles as a hybrid method to induce enhanced photothermal and photodynamic therapies. Full article

Cerenkov-induced photodynamic therapy (CR-PDT) with the use of Gallium-68 (⁶⁸Ga) as an unsealed radioactive source has been proposed as an alternative strategy to X-ray-induced photodynamic therapy (X-PDT). This new strategy still aims to produce a photodynamic effect with the use of nanoparticles, namely, AGuIX. Recently, we replaced Gd from the AGuIX@ platform with Terbium (Tb) as a nanoscintillator and added 5-(4-carboxyphenyl succinimide ester)-10,15,20-triphenylporphyrin (P1) as a photosensitizer (referred to as AGuIX@Tb-P1). Although Cerenkov luminescence from ⁶⁸Ga positrons is involved in nanoscintillator and photosensitizer activation, the cytotoxic effect obtained by PDT remains controversial. Herein, we tested whether free ⁶⁸Ga could substitute X-rays of X-PDT to obtain a cytotoxic phototherapeutic effect. Results were compared with those obtained with AGuIX@Gd-P1 nanoparticles. We showed, by Monte Carlo simulations, the contribution of Tb scintillation in P1 activation by an energy transfer between Tb and P1 after Cerenkov radiation, compared to the Gd-based nanoparticles. We confirmed the involvement of the type II PDT reaction during ⁶⁸Ga-mediated Cerenkov luminescence, id est, the transfer of photon to AGuIX@Tb-P1 which, in turn, generated P1-mediated singlet oxygen. The effect of ⁶⁸Ga on cell survival was studied by clonogenic assays using human glioblastoma U-251 MG cells. Exposure of pre-treated cells with AGuIX@Tb-P1 to ⁶⁸Ga resulted in the decrease in cell clone formation, unlike AGuIX@Gd-P1. We conclude that CR-PDT could be an alternative of X-PDT. Full article

Hypoxia in solid tumors is associated with poor prognosis, increased aggressiveness, and strong resistance to therapeutics, making accurate monitoring of hypoxia important. Several imaging modalities have been used to study hypoxia, but each modality has inherent limitations. The use of a second modality can compensate for the limitations and validate the results of any single imaging modality. In this review, we describe dual-mode imaging systems for the detection of hypoxia that have been reported since the start of the 21st century. First, we provide a brief overview of the hallmarks of hypoxia used for imaging and the imaging modalities used to detect hypoxia, including optical imaging, ultrasound imaging, photoacoustic imaging, single-photon emission tomography, X-ray computed tomography, positron emission tomography, Cerenkov radiation energy transfer imaging, magnetic resonance imaging, electron paramagnetic resonance imaging, magnetic particle imaging, and surface-enhanced Raman spectroscopy, and mass spectrometric imaging. These overviews are followed by examples of hypoxia-relevant imaging using a mixture of probes for complementary single-mode imaging techniques. Then, we describe dual-mode molecular switches that are responsive in multiple imaging modalities to at least one hypoxia-induced pathological change. Finally, we offer future perspectives toward dual-mode imaging of hypoxia and hypoxia-induced pathophysiological changes in tumor microenvironments. Full article

We exploited the potential of radiation-induced emissions (RIEs) in the visible domain of a nitrogen-doped, silica-based, multimode optical fiber to monitor the very high dose rates associated with experiments at different pulsed X-ray facilities. We also tested this sensor at lower dose rates associated with steady-state X-ray irradiation machines (up to 100 keV photon energy, mean energy of 40 keV). For transient exposures, dedicated experimental campaigns were performed at ELSA (Electron et Laser, Source X et Applications) and ASTERIX facilities from CEA (Commissariat à l’Energie Atomique—France) to characterize the RIE of this fiber when exposed to X-ray pulses with durations of a few µs or ns. These facilities provide very large dose rates: in the order of MGy(SiO₂)/s for the ELSA facility (up to 19 MeV photon energy) and GGy(SiO₂)/s for the ASTERIX facility (up to 1 MeV). In both cases, the RIE intensities, mostly explained by the fiber radioluminescence (RIL) around 550 nm, with a contribution from Cerenkov at higher fluxes, linearly depend on the dose rates normalized to the pulse duration delivered by the facilities. By comparing these high dose rate results and those acquired under low-dose rate steady-state X-rays (only RIL was present), we showed that the RIE of this multimode optical fiber linearly depends on the dose rate over an ultra-wide dose rate range from 10⁻² Gy(SiO₂)/s to a few 10⁹ Gy(SiO₂)/s and photons with energy in the range from 40 keV to 19 MeV. These results demonstrate the high potential of this class of radiation monitors for beam monitoring at very high dose rates in a very large variety of facilities as future FLASH therapy facilities. Full article

With the continued development of nanomaterials over the past two decades, specialized photonanomedicines (light-activable nanomedicines, PNMs) have evolved to become excitable by alternative energy sources that typically penetrate tissue deeper than visible light. These sources include electromagnetic radiation lying outside the visible near-infrared spectrum, high energy particles, and acoustic waves, amongst others. Various direct activation mechanisms have leveraged unique facets of specialized nanomaterials, such as upconversion, scintillation, and radiosensitization, as well as several others, in order to activate PNMs. Other indirect activation mechanisms have leveraged the effect of the interaction of deeply penetrating energy sources with tissue in order to activate proximal PNMs. These indirect mechanisms include sonoluminescence and Cerenkov radiation. Such direct and indirect deep-tissue activation has been explored extensively in the preclinical setting to facilitate deep-tissue anticancer photodynamic therapy (PDT); however, clinical translation of these approaches is yet to be explored. This review provides a summary of the state of the art in deep-tissue excitation of PNMs and explores the translatability of such excitation mechanisms towards their clinical adoption. A special emphasis is placed on how current clinical instrumentation can be repurposed to achieve deep-tissue PDT with the mechanisms discussed in this review, thereby further expediting the translation of these highly promising strategies. Full article

We investigated in this work the radioluminescence properties of a Ce-doped multimode silica-based optical fiber (core diameter of 50 µm) manufactured by the sol–gel technique when exposed to the high-energy X-rays (~600 keV) of the ORIATRON facility of CEA. We demonstrated its potential to monitor in real-time the beam characteristics of this facility that can either operate in a pulsed regime (pulse duration of 4.8 µs, maximum repetition rate of 250 Hz) or in a quasi-continuous mode. The radiation-induced emission (radioluminescence and a minor Cerenkov contribution) linearly grew with the dose rate in the 15–130 mGy(SiO₂)/s range, and the afterglow measured after each pulse was sufficiently limited to allow a clear measurement of pulse trains. A sensor with ~11 cm of sensitive Ce-doped fiber spliced to rad-hard fluorine-doped optical fiber, for the emitted light transport to the photomultiplier tube, exhibited interesting beam monitoring performance, even if the Cerenkov emission in the transport fiber was also considered (~5% of the signal). The beam monitoring potential of this class of optical fiber was demonstrated for such facilities and the possibilities of extending the dose rate range are discussed based on possible architecture choices such as fiber type, length or size. Full article

The present work analyses a hybrid free electron laser (FEL) scheme where the oscillator is based on a radiation source operating with a slow-wave guiding structure as, for instance, a Cerenkov FEL or a Smith–Purcell FEL. Such devices, often running in transverse magnetic (TM) modes, present a longitudinal electric field which can easily affect the longitudinal electrons’ velocities, inducing an energy modulation on the beam. Such a modulation, properly controlled, can induce a strong radiation emission in a magnetic undulator properly designed to operate as a radiator. General considerations will be exposed together with a practical numerical example in the far infrared region of the spectrum. Full article

Ovarian cancer (OC) metastases frequently occur through peritoneal dissemination, and they contribute to difficulties in treatment. While photodynamic therapy (PDT) has the potential to treat OC, its use is often limited by tissue penetration depth and tumor selectivity. Herein, we combined Cerenkov radiation (CR) emitted by ¹⁸F-FDG accumulated in tumors as an internal light source and several photosensitizer (PS) candidates with matched absorption bands, including Verteporfin (VP), Chlorin e6 (Ce6) and 5′-Aminolevulinic acid (5′-ALA), to evaluate the anti-tumor efficacy. The in vitro effect of CR-induced PDT (CR-PDT) was evaluated using a cell viability assay, and the efficiency of PS was assessed by measuring the singlet oxygen production. An intraperitoneal ES2 OC mouse model was used for in vivo evaluation of CR-PDT. Positron emission tomography (PET) imaging and bioluminescence-based imaging were performed to monitor the biologic uptake of ¹⁸F-FDG and the therapeutic effect. The in vitro studies demonstrated Ce6 and VP to be more effective PSs for CR-PDT. Moreover, VP was more efficient in the generation of singlet oxygen and continued for a long time when exposed to fluoro-18 (¹⁸F). Combining CR emitted by ¹⁸F-FDG and VP treatment not only significantly suppressed tumor growth, but also prolonged median survival times compared to either monotherapy. Full article

Photodynamic therapy (PDT) is a promising therapeutic strategy for cancers where surgery and radiotherapy cannot be effective. PDT relies on the photoactivation of photosensitizers, most of the time by lasers to produced reactive oxygen species and notably singlet oxygen. The major drawback of this strategy is the weak light penetration in the tissues. To overcome this issue, recent studies proposed to generate visible light in situ with radioactive isotopes emitting charged particles able to produce Cerenkov radiation. In vitro and preclinical results are appealing, but the existence of a true, lethal phototherapeutic effect is still controversial. In this article, we have reviewed previous original works dealing with Cerenkov-induced PDT (CR-PDT). Moreover, we propose a simple analytical equation resolution to demonstrate that Cerenkov light can potentially generate a photo-therapeutic effect, although most of the Cerenkov photons are emitted in the UV-B and UV-C domains. We suggest that CR-PDT and direct UV-tissue interaction act synergistically to yield the therapeutic effect observed in the literature. Moreover, adding a nanoscintillator in the photosensitizer vicinity would increase the PDT efficacy, as it will convert Cerenkov UV photons to light absorbed by the photosensitizer. Full article

Cerenkov luminescence imaging and Cerenkov photodynamic therapy have been developed in recent years to exploit the Cerenkov radiation (CR) generated by radioisotopes, frequently used in Nuclear Medicine, to diagnose and fight cancer lesions. For in vivo detection, the endpoint energy of the radioisotope and, thus, the total number of the emitted Cerenkov photons, represents a very important variable and explains why, for example, ⁶⁸Ga is better than ¹⁸F. However, it was also found that the scintillation process is an important mechanism for light production. Nanotechnology represents the most important field, providing nanosctructures which are able to shift the UV-blue emission into a more suitable wavelength, with reduced absorption, which is useful especially for in vivo imaging and therapy applications. Nanoparticles can be made, loaded or linked to fluorescent dyes to modify the optical properties of CR radiation. They also represent a useful platform for therapeutic agents, such as photosensitizer drugs for the production of reactive oxygen species (ROS). Generally, NPs can be spaced by CR sources; however, for in vivo imaging applications, NPs bound to or incorporating radioisotopes are the most interesting nanocomplexes thanks to their high degree of mutual colocalization and the reduced problem of false uptake detection. Moreover, the distance between the NPs and CR source is crucial for energy conversion. Here, we review the principal NPs proposed in the literature, discussing their properties and the main results obtained by the proponent experimental groups. Full article

When exposed to air, alpha particles cause the production of light by exciting the molecules surrounding them. This light, the radioluminescence, is indicative of the presence of alpha radiation, thus allowing for the optical sensing of alpha radiation from distances larger than the few centimeters an alpha particle can travel in air. While the mechanics of radioluminescence in air and other gas compositions is relatively well understood, the same cannot be said about the radioluminescence properties of liquids. Better understanding of the radioluminescence properties of liquids is essential to design methods for the detection of radioactively contaminated liquids by optical means. In this article, we provide radioluminescence images of Am-241 dissolved in aqueous nitric acid ( ${\mathrm{HNO}}_3$ ) solution and present the recorded radioluminescence spectrum with a maximum between $350\mathrm{nm}$ and $400\mathrm{nm}$ , and a steep decrease at the short wavelength side of the maximum. The shape of the spectrum resembles a luminescence process rather than Cerenkov light, bremsstrahlung, or other mechanisms with broadband emission. We show that the amount of light produced is about 150 times smaller compared to that of the same amount of Am-241 in air. The light production in the liquid is evenly distributed throughout the sample volume with a slight increase on the surface of the liquid. The radioluminescence intensity is shown to scale linearly with the Am-241 concentration and not be affected by the ${\mathrm{HNO}}_3$ concentration. Full article

In a Lorentz-violating quantum field theory, the energy-momentum relations for the field quanta are typically modified. This affects the kinematics, and processes that are normally forbidden may become allowed. One reaction that clearly becomes kinematically possible when photons’ phase speeds are less than 1 is vacuum Cerenkov radiation. However, in spite of expectations, and in defiance of phase space estimates, a electromagnetic Chern–Simons theory with a timelike Lorentz violation coefficient does not feature any energy losses through Cerenkov emission. There is an unexpected cancelation, made possible by the existence of unstable long-wavelength modes of the field. The fact that the theory possesses a more limited form of gauge symmetry than conventional electrodynamics also plays a role. Full article

In this study, a wavelength shifting fiber that shifts ultra-violet and blue light to green light was employed as a sensor probe of a fiber-optic Cerenkov radiation sensor. In order to characterize Cerenkov radiation generated in the developed wavelength shifting fiber and a plastic optical fiber, spectra and intensities of Cerenkov radiation were measured with a spectrometer. The spectral peaks of light outputs from the wavelength shifting fiber and the plastic optical fiber were measured at wavelengths of 500 and 510 nm, respectively, and the intensity of transmitted light output of the wavelength shifting fiber was 22.2 times higher than that of the plastic optical fiber. Also, electron fluxes and total energy depositions of gamma-ray beams generated from a Co-60 therapy unit were calculated according to water depths using the Monte Carlo N-particle transport code. The relationship between the fluxes of electrons over the Cerenkov threshold energy and the energy depositions of gamma-ray beams from the Co-60 unit is a near-identity function. Finally, percentage depth doses for the gamma-ray beams were obtained using the fiber-optic Cerenkov radiation sensor, and the results were compared with those obtained by an ionization chamber. The average dose difference between the results of the fiber-optic Cerenkov radiation sensor and those of the ionization chamber was about 2.09%. Full article