Beyond Average : a-Particle Distribution and Dose Heterogeneity in Bone Metastatic Prostate Cancer
(2024) In Journal of Nuclear Medicine 65(2). p.245-251- Abstract
a-particle emitters are emerging as a potent modality for disseminated cancer therapy because of their high linear energy transfer and localized absorbed dose profile. Despite great interest and pharmaceutical development, there is scant information on the distribution of these agents at the scale of the a-particle pathlength. We sought to determine the distribution of clinically approved [223Ra]RaCl2 in bone metastatic castration-resistant prostate cancer at this resolution, for the first time to our knowledge, to inform activity distribution and dose at the near-cell scale. Methods: Biopsy specimens and blood were collected from 7 patients 24 h after administration. 223Ra activity in each sample was... (More)
a-particle emitters are emerging as a potent modality for disseminated cancer therapy because of their high linear energy transfer and localized absorbed dose profile. Despite great interest and pharmaceutical development, there is scant information on the distribution of these agents at the scale of the a-particle pathlength. We sought to determine the distribution of clinically approved [223Ra]RaCl2 in bone metastatic castration-resistant prostate cancer at this resolution, for the first time to our knowledge, to inform activity distribution and dose at the near-cell scale. Methods: Biopsy specimens and blood were collected from 7 patients 24 h after administration. 223Ra activity in each sample was recorded, and the microstructure of biopsy specimens was analyzed by micro-CT. Quantitative autoradiography and histopathology were segmented and registered with an automated procedure. Activity distributions by tissue compartment and dosimetry calculations based on the MIRD formalism were performed. Results: We revealed the activity distribution differences across and within patient samples at the macro- and microscopic scales. Microdistribution analysis confirmed localized high-activity regions in a background of low-activity tissue. We evaluated heterogeneous a-particle emission distribution concentrated at bone–tissue interfaces and calculated spatially nonuniform absorbed-dose profiles. Conclusion: Primary patient data of radiopharmaceutical therapy distribution at the small scale revealed that 223Ra uptake is nonuniform. Dose estimates present both opportunities and challenges to enhance patient outcomes and are a first step toward personalized treatment approaches and improved understanding of a-particle radiopharmaceutical therapies.
(Less)
- author
- organization
- publishing date
- 2024-02-10
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Ra, a-particle, autoradiography, biopsy, dosimetry
- in
- Journal of Nuclear Medicine
- volume
- 65
- issue
- 2
- pages
- 7 pages
- publisher
- Society of Nuclear Medicine
- external identifiers
-
- pmid:38124163
- scopus:85184282069
- ISSN
- 0161-5505
- DOI
- 10.2967/jnumed.123.266571
- language
- English
- LU publication?
- yes
- id
- a2d78c04-150b-4c5a-b4f6-9c2f76419ce8
- date added to LUP
- 2024-02-22 14:21:41
- date last changed
- 2024-04-23 16:14:04
@article{a2d78c04-150b-4c5a-b4f6-9c2f76419ce8,
abstract = {{<p>a-particle emitters are emerging as a potent modality for disseminated cancer therapy because of their high linear energy transfer and localized absorbed dose profile. Despite great interest and pharmaceutical development, there is scant information on the distribution of these agents at the scale of the a-particle pathlength. We sought to determine the distribution of clinically approved [<sup>223</sup>Ra]RaCl<sub>2</sub> in bone metastatic castration-resistant prostate cancer at this resolution, for the first time to our knowledge, to inform activity distribution and dose at the near-cell scale. Methods: Biopsy specimens and blood were collected from 7 patients 24 h after administration. <sup>223</sup>Ra activity in each sample was recorded, and the microstructure of biopsy specimens was analyzed by micro-CT. Quantitative autoradiography and histopathology were segmented and registered with an automated procedure. Activity distributions by tissue compartment and dosimetry calculations based on the MIRD formalism were performed. Results: We revealed the activity distribution differences across and within patient samples at the macro- and microscopic scales. Microdistribution analysis confirmed localized high-activity regions in a background of low-activity tissue. We evaluated heterogeneous a-particle emission distribution concentrated at bone–tissue interfaces and calculated spatially nonuniform absorbed-dose profiles. Conclusion: Primary patient data of radiopharmaceutical therapy distribution at the small scale revealed that <sup>223</sup>Ra uptake is nonuniform. Dose estimates present both opportunities and challenges to enhance patient outcomes and are a first step toward personalized treatment approaches and improved understanding of a-particle radiopharmaceutical therapies.</p>}},
author = {{Benabdallah, Nadia and Lu, Peng and Abou, Diane S. and Zhang, Hanwen and Ulmert, David and Hobbs, Robert F. and Gay, Hiram A. and Simons, Brian W. and Saeed, Muhammad A. and Rogers, Buck E. and Jha, Abhinav K. and Tai, Yuan Chuan and Malone, Christopher D. and Ippolito, Joseph E. and Michalski, Jeff and Jennings, Jack W. and Baumann, Brian C. and Pachynski, Russell K. and Thorek, Daniel L.J.}},
issn = {{0161-5505}},
keywords = {{Ra; a-particle; autoradiography; biopsy; dosimetry}},
language = {{eng}},
month = {{02}},
number = {{2}},
pages = {{245--251}},
publisher = {{Society of Nuclear Medicine}},
series = {{Journal of Nuclear Medicine}},
title = {{Beyond Average : a-Particle Distribution and Dose Heterogeneity in Bone Metastatic Prostate Cancer}},
url = {{http://dx.doi.org/10.2967/jnumed.123.266571}},
doi = {{10.2967/jnumed.123.266571}},
volume = {{65}},
year = {{2024}},
}