| 1. |
- Abou, Diane S., et al.
(författare)
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Improved 223Ra Therapy with Combination Epithelial Sodium Channel Blockade
- 2021
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 62:12, s. 1751-1758
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Tidskriftsartikel (refereegranskat)abstract
- [223Ra]RaCl2 is the first approved a-particle-emitting therapy and is indicated for treatment of bonemetastatic castration-resistant prostate cancer. Approximately half the dose is absorbed into the gastrointestinal tract within minutes of administration, limiting disease-site uptake and contributing to toxicity. Here,we investigated the role of enteric ion channels and their modulation for improved therapeutic efficacy and reduced side effects. Methods: Using primary human duodenal organoids (enteroids) asin vitromodelsof the functionalgastrointestinal epithelium, we found that amiloride (epithelial sodium ion channel blocker) and NS-1619 (K+ channel activator) presented significant effects in 223Ramembranal transport.Radioactivedrugdistributionwas evaluated for lead combinations in vivo and in osteosarcoma and prostate cancermodels.Results:Amiloride shifted 223Ra uptake in vivo fromthe gut and nearly doubled the uptake at sites of bone remodeling. Bone tumor growth inhibition with the combination as measured by bioluminescent imaging and radiographywas significantly greater than that with single agents alone, and the combination resulted in noweight loss.Conclusion: This combination of approved agentsmay readily be implemented as a clinical approach to improve the outcomes of bonemetastatic cancer patients with the benefit of ameliorated tolerability. COPYRIGHT
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| 2. |
- Abou, Diane S., et al.
(författare)
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Preclinical Single Photon Emission Computed Tomography of Alpha Particle-Emitting Radium-223
- 2020
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Ingår i: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 35:7, s. 520-529
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Dose optimization and pharmacokinetic evaluation of α-particle emitting radium-223 dichloride (223RaCl2) by planar γ-camera or single photon emission computed tomography (SPECT) imaging are hampered by the low photon abundance and injected activities. In this study, we demonstrate SPECT of 223Ra using phantoms and small animal in vivo models. Methods: Line phantoms and mice bearing 223Ra were imaged using a dedicated small animal SPECT by detecting the low-energy photon emissions from 223Ra. Localization of the therapeutic agent was verified by whole-body and whole-limb autoradiography and its radiobiological effect confirmed by immunofluorescence. Results: A state-of-the-art commercial small animal SPECT system equipped with a highly sensitive collimator enables collection of sufficient counts for three-dimensional reconstruction at reasonable administered activities and acquisition times. Line sources of 223Ra in both air and in a water scattering phantom gave a line spread function with a full-width-at-half-maximum of 1.45 mm. Early and late-phase imaging of the pharmacokinetics of the radiopharmaceutical were captured. Uptake at sites of active bone remodeling was correlated with DNA damage from the α particle emissions. Conclusions: This work demonstrates the capability to noninvasively define the distribution of 223RaCl2, a recently approved α-particle-emitting radionuclide. This approach allows quantitative assessment of 223Ra distribution and may assist radiation-dose optimization strategies to improve therapeutic response and ultimately to enable personalized treatment planning.
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| 3. |
- Purdum, Josiah N., et al.
(författare)
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Time-series and Phase-curve Photometry of the Episodically Active Asteroid (6478) Gault in a Quiescent State Using APO, GROWTH, P200, and ZTF
- 2021
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 911:2
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Tidskriftsartikel (refereegranskat)abstract
- We observed the episodically active asteroid (6478) Gault in 2020 with multiple telescopes in Asia and North America and found that it is no longer active after its recent outbursts at the end of 2018 and the start of 2019. The inactivity during this apparition allowed us to measure the absolute magnitude of Gault of H ( r ) = 14.63 +/- 0.02, G ( r ) = 0.21 +/- 0.02 from our secular phase-curve observations. In addition, we were able to constrain Gault's rotation period using time-series photometric lightcurves taken over 17 hr on multiple days in 2020 August, September, and October. The photometric lightcurves have a repeating less than or similar to 0.05 mag feature suggesting that (6478) Gault has a rotation period of similar to 2.5 hr and may have a semispherical or top-like shape, much like the near-Earth asteroids Ryugu and Bennu. The rotation period of similar to 2.5 hr is near the expected critical rotation period for an asteroid with the physical properties of (6478) Gault, suggesting that its activity observed over multiple epochs is due to surface mass shedding from its fast rotation spin-up by the Yarkovsky-O'Keefe-Radzievskii-Paddack effect.
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| 4. |
- van Velzen, Sjoert, et al.
(författare)
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Seventeen Tidal Disruption Events from the First Half of ZTF Survey Observations : Entering a New Era of Population Studies
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 908:1
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Tidskriftsartikel (refereegranskat)abstract
- While tidal disruption events (TDEs) have long been heralded as laboratories for the study of quiescent black holes, the small number of known TDEs and uncertainties in their emission mechanism have hindered progress toward this promise. Here we present 17 new TDEs that have been detected recently by the Zwicky Transient Facility along with Swift UV and X-ray follow-up observations. Our homogeneous analysis of the optical/UV light curves, including 22 previously known TDEs from the literature, reveals a clean separation of light-curve properties with spectroscopic class. The TDEs with Bowen fluorescence features in their optical spectra have smaller blackbody radii, lower optical luminosities, and higher disruption rates compared to the rest of the sample. The small subset of TDEs that show only helium emission lines in their spectra have the longest rise times, the highest luminosities, and the lowest rates. A high detection rate of Bowen lines in TDEs with small photometric radii could be explained by the high density that is required for this fluorescence mechanism. The stellar debris can provide a source for this dense material. Diffusion of photons through this debris may explain why the rise and fade timescale of the TDEs in our sample are not correlated. We also report, for the first time, the detection of soft X-ray flares from a TDE on similar to day timescales. Based on the fact that the X-ray flares peak at a luminosity similar to the optical/UV blackbody luminosity, we attribute them to brief glimpses through a reprocessing layer that otherwise obscures the inner accretion flow.
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