Tumor Control Probability and Small-Scale Monte Carlo Dosimetry : Effects of Heterogenous Intratumoral Activity Distribution in Radiopharmaceutical Therapy
(2023) In Journal of Nuclear Medicine 64(10). p.1-6- Abstract
In radiopharmaceutical therapy, intratumoral uptake of radioactivity usually leads to heterogeneous absorbed dose distribution. The likelihood of treatment success can be estimated with the tumor control probability (TCP), which requires accurate dosimetry, estimating the absorbed dose rate per unit activity to individual tumor cells. Methods: Xenograft cryosections of the prostate cancer cell line LNCaP treated with [177Lu]Lu-PSMA-617 were evaluated with digital autoradiography and stained with hematoxylin and eosin. The digital autoradiography images were used to define the source in a Monte Carlo simulation of the absorbed dose, and the stained sections were used to detect the position of cell nuclei to relate the... (More)
In radiopharmaceutical therapy, intratumoral uptake of radioactivity usually leads to heterogeneous absorbed dose distribution. The likelihood of treatment success can be estimated with the tumor control probability (TCP), which requires accurate dosimetry, estimating the absorbed dose rate per unit activity to individual tumor cells. Methods: Xenograft cryosections of the prostate cancer cell line LNCaP treated with [177Lu]Lu-PSMA-617 were evaluated with digital autoradiography and stained with hematoxylin and eosin. The digital autoradiography images were used to define the source in a Monte Carlo simulation of the absorbed dose, and the stained sections were used to detect the position of cell nuclei to relate the intratumoral absorbed dose heterogeneity to the cell density. Simulations were performed for 225Ac, 177Lu, and 90Y. TCP was calculated to estimate the mean necessary injected activity for a high TCP. A hypothetical case of activity mainly taken up on the tumor borders was generated and used to simulate the absorbed dose. Results: The absorbed dose per decay to tumor cells was calculated from the staining and simulation results to avoid underestimating the tumor response from low absorbed doses in tumor regions with low cell density. The mean of necessary injected activity to reach a 90% TCP for 225Ac, 177Lu, and 90Y was found to be 18.3 kBq (range, 18–22 kBq), 24.3 MBq (range, 20–29 MBq), and 5.6 MBq (range, 5–6 MBq), respectively. Conclusion: To account for the heterogeneous absorbed dose generated from nonuniform intratumoral activity uptake, dosimetry models can estimate the mean necessary activity to reach a sufficient TCP for treatment response. This approach is necessary to accurately evaluate the efficacy of suggested radiopharmaceuticals for therapy.
(Less)
- author
- Mellhammar, Emma LU ; Dahlbom, Magnus ; Vilhelmsson-Timmermand, Oskar LU and Strand, Sven Erik LU
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- digital autoradiography, heterogeneity, Monte Carlo dosimetry simulation, radiopharmaceutical therapy, tumor control probability
- in
- Journal of Nuclear Medicine
- volume
- 64
- issue
- 10
- pages
- 6 pages
- publisher
- Society of Nuclear Medicine
- external identifiers
-
- pmid:37934033
- scopus:85173556998
- ISSN
- 0161-5505
- DOI
- 10.2967/jnumed.123.265523
- language
- English
- LU publication?
- yes
- id
- 1c902be4-779a-4e86-b17e-057ff39158ad
- date added to LUP
- 2023-12-06 13:54:21
- date last changed
- 2024-04-19 08:29:57
@article{1c902be4-779a-4e86-b17e-057ff39158ad,
abstract = {{<p>In radiopharmaceutical therapy, intratumoral uptake of radioactivity usually leads to heterogeneous absorbed dose distribution. The likelihood of treatment success can be estimated with the tumor control probability (TCP), which requires accurate dosimetry, estimating the absorbed dose rate per unit activity to individual tumor cells. Methods: Xenograft cryosections of the prostate cancer cell line LNCaP treated with [<sup>177</sup>Lu]Lu-PSMA-617 were evaluated with digital autoradiography and stained with hematoxylin and eosin. The digital autoradiography images were used to define the source in a Monte Carlo simulation of the absorbed dose, and the stained sections were used to detect the position of cell nuclei to relate the intratumoral absorbed dose heterogeneity to the cell density. Simulations were performed for <sup>225</sup>Ac, <sup>177</sup>Lu, and <sup>90</sup>Y. TCP was calculated to estimate the mean necessary injected activity for a high TCP. A hypothetical case of activity mainly taken up on the tumor borders was generated and used to simulate the absorbed dose. Results: The absorbed dose per decay to tumor cells was calculated from the staining and simulation results to avoid underestimating the tumor response from low absorbed doses in tumor regions with low cell density. The mean of necessary injected activity to reach a 90% TCP for <sup>225</sup>Ac, <sup>177</sup>Lu, and <sup>90</sup>Y was found to be 18.3 kBq (range, 18–22 kBq), 24.3 MBq (range, 20–29 MBq), and 5.6 MBq (range, 5–6 MBq), respectively. Conclusion: To account for the heterogeneous absorbed dose generated from nonuniform intratumoral activity uptake, dosimetry models can estimate the mean necessary activity to reach a sufficient TCP for treatment response. This approach is necessary to accurately evaluate the efficacy of suggested radiopharmaceuticals for therapy.</p>}},
author = {{Mellhammar, Emma and Dahlbom, Magnus and Vilhelmsson-Timmermand, Oskar and Strand, Sven Erik}},
issn = {{0161-5505}},
keywords = {{digital autoradiography; heterogeneity; Monte Carlo dosimetry simulation; radiopharmaceutical therapy; tumor control probability}},
language = {{eng}},
number = {{10}},
pages = {{1--6}},
publisher = {{Society of Nuclear Medicine}},
series = {{Journal of Nuclear Medicine}},
title = {{Tumor Control Probability and Small-Scale Monte Carlo Dosimetry : Effects of Heterogenous Intratumoral Activity Distribution in Radiopharmaceutical Therapy}},
url = {{http://dx.doi.org/10.2967/jnumed.123.265523}},
doi = {{10.2967/jnumed.123.265523}},
volume = {{64}},
year = {{2023}},
}