Preclinical Single Photon Emission Computed Tomography of Alpha Particle-Emitting Radium-223
(2020) In Cancer Biotherapy and Radiopharmaceuticals 35(7). p.520-529- 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... (More)
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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- author
- Abou, Diane S. ; Rittenbach, Andrew ; Tomlinson, Ryan E. ; Finley, Paige A. ; Tsui, Benjamin ; Simons, Brian W. ; Jha, Abhinav K. ; Ulmert, David LU ; Riddle, Ryan C. and Thorek, Daniel L.J.
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- molecular imaging, pharmacokinetics, theranostics, α-particle radiotherapy
- in
- Cancer Biotherapy and Radiopharmaceuticals
- volume
- 35
- issue
- 7
- pages
- 10 pages
- publisher
- Mary Ann Liebert, Inc.
- external identifiers
-
- pmid:32182119
- scopus:85086781230
- ISSN
- 1084-9785
- DOI
- 10.1089/cbr.2019.3308
- language
- English
- LU publication?
- yes
- id
- 7489223b-0d6e-4e5f-ac49-dcdafd61a734
- date added to LUP
- 2021-01-08 12:59:06
- date last changed
- 2024-05-17 01:00:22
@article{7489223b-0d6e-4e5f-ac49-dcdafd61a734,
abstract = {{<p>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. </p>}},
author = {{Abou, Diane S. and Rittenbach, Andrew and Tomlinson, Ryan E. and Finley, Paige A. and Tsui, Benjamin and Simons, Brian W. and Jha, Abhinav K. and Ulmert, David and Riddle, Ryan C. and Thorek, Daniel L.J.}},
issn = {{1084-9785}},
keywords = {{molecular imaging; pharmacokinetics; theranostics; α-particle radiotherapy}},
language = {{eng}},
number = {{7}},
pages = {{520--529}},
publisher = {{Mary Ann Liebert, Inc.}},
series = {{Cancer Biotherapy and Radiopharmaceuticals}},
title = {{Preclinical Single Photon Emission Computed Tomography of Alpha Particle-Emitting Radium-223}},
url = {{http://dx.doi.org/10.1089/cbr.2019.3308}},
doi = {{10.1089/cbr.2019.3308}},
volume = {{35}},
year = {{2020}},
}