Olga Volotskova

Synergistic assembly of heavy metal clusters and luminescent organic bridging ligands in metal-organic frameworks for highly efficient X-ray scintillation.

We have designed two metal–organic frameworks (MOFs) to efficiently convert X-ray to visible-light luminescence. The MOFs are constructed from M6(μ3-O)4(μ3-OH)4(carboxylate)12 (M = Hf or Zr) secondary building units (SBUs) and anthracene-based dicarboxylate bridging ligands. The high atomic number of Zr and Hf in the SBUs serves as effective X-ray antenna by absorbing X-ray photons and converting them to fast electrons through the photoelectric effect. The generated electrons then excite multiple anthracene-based emitters in the MOF through inelastic scattering, leading to efficient generation of detectable photons in the visible spectrum. The MOF materials thus serve as efficient X-ray scintillators via synergistic X-ray absorption by the metal-cluster SBUs and optical emission by the bridging ligands.

Hard X-ray-induced optical luminescence via biomolecule-directed metal clusters.

Here, we demonstrate that biomolecule-directed metal clusters are applicable in the study of hard X-ray excited optical luminescence, promising a new direction in the development of novel X-ray-activated imaging probes.

Efficient Radioisotope Energy Transfer by Gold Nanoclusters for Molecular Imaging

Beta-emitting isotopes Fluorine-18 and Yttrium-90 are tested for their potential to stimulate gold nanoclusters conjugated with blood serum proteins (AuNCs). AuNCs excited by either medical radioisotope are found to be highly effective ionizing radiation energy transfer mediators, suitable for in vivo optical imaging. AuNCs synthesized with protein templates convert beta-decaying radioisotope energy into tissue-penetrating optical signals between 620 and 800 nm. Optical signals are not detected from AuNCs incubated with Technetium-99m, a pure gamma emitter that is used as a control. Optical emission from AuNCs is not proportional to Cerenkov radiation, indicating that the energy transfer between the radionuclide and AuNC is only partially mediated by Cerenkov photons. A direct Coulombic interaction is proposed as a novel and significant mechanism of energy transfer between decaying radionuclides and AuNCs.

WE-AB-BRB-02: Development of a Micro-Sized Dosimeter for Real-Time Dose Monitoring and Small Field Dosimetry

Purpose: To investigate a miniature optical dosimeter for real-time, high-resolution dosimetry, and explore its potential applications for in vivo measurements and small field dosimetry. Methods: A micro-sized hemispherical (400 µm radius) scintillating detector was constructed from lanthanide activated phosphors doped with Europium (GOS:Eu) and encapsulated in a 17 gauge plastic catheter. A photon counting PMT and CCD-chip spectrometer were used to detect signals emitted from the detector. A single band-passing spectral approach (630nm) was implemented to discriminate the micro-phosphor optical signal from background signals (Cerenkov radiation) in the optical fiber. To test real-time monitoring capabilities, a 3D-printed phantom was used to detect an 192Ir HDR brachytherapy source at locations ranging from 1 to 4 cm radially and 12 cm along the travel axis of the HDR wire. To test the application of the micro-sized detector for small field dosimetry, the linearity of detector was characterized through irradiation of 6MV photon beam at dose-rates ranging from 100 to 600 MU, and the effect of field size was characterized through detections of beams ranging from 30×30 to 1×1 cm2 size. Results: With a 1 second integration time for the spectrometer, the recorded measurements indicated that the micro-sized detector allowed accurate detection of source position at distances of up to 6 cm along the axis of travel in water. EB measurements showed that the detected signal was linearly correlated with dose rate (R^2 = 0.99). The crossbeam profile was determined with a step size of ∼500 µm. Conclusion: Miniaturization of optical dosimeters is shown to be possible through the construction of lanthanide activated doped phosphors detectors. The small size of the detector makes it amenable to a variety of applications, including real-time dose delivery verification during HDR brachytherapy and EB beam calibrations in small fields.

TH-C-17A-02: New Radioluminescence Strategies Based On CRET (Cerenkov Radiation Energy Transfer) for Imaging and Therapy

PURPOSE Cerenkov photons are produced when charged particles, emitted from radionuclides, travel through a media with a speed greater than that of the light in the media. Cerenkov radiation is mostly in the UV/Blue region and, thus, readily absorbed by biological tissue. Cerenkov Radiation Energy Transfer (CRET) is a wavelength-shifting phenomenon from blue Cerenkov light to more penetrating red wavelengths. We demonstrate the feasibility of in-depth imaging of CRET light originating from radionuclides realized by down conversion of gold nanoclusters (AuNCs, a novel particle composed of few atoms of gold coated with serum proteins) in vivo. METHODS Bovine Serum Albumin, Human Serum Albumin and Transferrin conjugated gold nanoclusters were synthesized, characterized and examined for CRET. Three different clinically used radiotracers: 18F-FDG, 90Y and 99mTc were used. Optical spectrum (440-750 nm) was recorded by sensitive bioluminescence imaging system at physiological temperature. Dose dependence (activity range from 0.5 up to 800uCi) and concentration dependence (0.01 to 1uM) studies were carried out. The compound was also imaged in a xenograft mouse model. RESULTS Only β+ and β--emitting radionuclides (18F-FDG, 90Y) are capable of CRET; no signal was found in 99mTc (γ-emitter). The emission peak of CRET by AuNCs was found to be ∼700 nm and was ∼3 fold times of background. In vitro studies showed a linear dependency between luminescence intensity and dose and concentration. CRET by gold nanoclusters was observed in xenografted mice injected with 100uCi of 18F-FDG. CONCLUSION The unique optical, transport and chemical properties of AuNCs (gold nanoclusters) make them ideal candidates for in-vivo imaging applications. Development of new molecular imaging probes will allow us to achieve substantially improved spatiotemporal resolution, sensitivity and specificity for tumor imaging and detection.

SU-E-QI-15: Single Point Dosimetry by Means of Cerenkov Radiation Energy Transfer (CRET)

PURPOSE Cerenkov light is generated when a charged particles with energy greater then 250 keV, moves faster than the speed of light in a given medium. Both x-ray photons and electrons produce optical Cerenkov photons during the static megavoltage linear accelerator (LINAC) operational mode. Recently, Cerenkov radiation gained considerable interest as possible candidate as a new imaging modality. Optical signals generated by Cerenkov radiation may act as a surrogate for the absorbed superficial radiation dose. We demonstrated a novel single point dosimetry method for megavoltage photon and electron therapy utilizing down conversion of Cerenkov photons. METHODS The custom build signal characterization system was used: a sample holder (probe) with adjacent light tight compartments was connected via fiber-optic cables to a photon counting photomultiplier tube (PMT). One compartment contains a medium only while the other contains medium and red-shifting nano-particles (Q-dots, nanoclusters). By taking the difference between the two signals (Cerenkov photons and CRET photons) we obtain a measure of the down-converted light, which we expect to be proportional to dose as measured with an adjacent ion chamber. Experimental results are compared to Monte Carlo simulations performed using the GEANT4 code. RESULTS The signal correlation between CR signal, CRET readings and dose produced by LINAC at a single point were investigated. The experimental results were compared with simulations. The dose linearity, signal to noise ratio and dose rate dependence were tested with custom build CRET based probe. CONCLUSION Performance characteristics of the proposed single point CRET based probe were evaluated. The direct use of the induced Cerenkov emission and CRET in an irradiated single point volume as an indirect surrogate for the imparted dose was investigated. We conclude that CRET is a promising optical based dosimetry method that offers advantages over those already proposed.

MO-D-141-07: X-Ray Activated Gold Nanoparticles for Tumor-Specific Molecular Imaging

PURPOSE X-ray radiography and computed tomography are commonly used anatomical imaging modalities still have significant shortcomings in sensitivity and specificity. Molecular imaging based on tumor-specific nanoparticles that can probe biochemical processes in vivo can provide characterization and identification of benign and malignant lesions on the cellular level. In particular, radioluminescent nanoparticles (RLNPs) are the ideal platform for X-ray-mediated imaging and synergistic therapy during radiation treatment. These unique particles can emit visible light under X-ray irradiation. However, existing RLNPs based on lanthanides may cause toxicity in vivo. Here we report new intriguing radioluminescent properties of a new type of nanoparticles made by arranging a small number of gold atoms. The objective of this work is to examine practical aspects of a new imaging modality: light emission and spectral emission characteristics. METHODS Bare gold nanoparticles (4 and 1.8 nm) and conjugated gold nanoparticles with size less than 2 nm (25 atoms size) were synthesized. Imaging was performed by irradiating the samples with X-ray (30-80 kVp, 10-30 mA) while acquiring 10 s frames with an EMCCD camera (Princeton Instruments, 300-900 nm). The samples were further characterized by using a custom PMT-based system. The spectral properties of the emission were measured under both optical and X-ray excitation using a sensitive spectrometer. RESULTS It was found that tested gold nanoparticles had different responses to x-ray excitation. Au25-BSA is the most promising candidate for x-ray luminescence imaging, with up to 4-6-fold increase in the optical signal compared to the controls. CONCLUSION In this work, it was first time demonstrated the optical detection of small atom number gold nanoparticles excited by x-ray source. Development of a new optical imaging probes will allow us to take advantage of the desirable features of optical molecular imaging and achieve substantially improved spatiotemporal resolution, sensitivity and specificity for tumor detection.