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Radionuclide spatial distribution and dose deposition for in vitro assessments of 212Pb‐αVCAM‐1 targeted alpha therapy.

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Title: Radionuclide spatial distribution and dose deposition for in vitro assessments of 212Pb‐αVCAM‐1 targeted alpha therapy.
Authors: Frelin‐Labalme, Anne‐Marie1 (AUTHOR) anne-marie.frelin@ganil.fr, Roger, Thomas1 (AUTHOR), Falzone, Nadia2 (AUTHOR), Quan Lee, Boon2 (AUTHOR), Sibson, Nicola R.2 (AUTHOR), Vallis, Katherine A.2 (AUTHOR), Bernaudin, Myriam3 (AUTHOR), Valable, Samuel3 (AUTHOR), Corroyer‐Dulmont, Aurélien2,3 (AUTHOR)
Source: Medical Physics. Mar2020, Vol. 47 Issue 3, p1317-1326. 10p.
Subjects: Monte Carlo method, Spatial distribution (Quantum optics), Radioisotopes, Silicon detectors, Alpha rhythm, Absorbed dose, Cell culture, Energy transfer
Abstract: Purpose: Targeted alpha therapy (TAT) takes advantage of the short‐range and high‐linear energy transfer of α‐particles and is increasingly used, especially for the treatment of metastatic lesions. Nevertheless, dosimetry of α‐emitters is challenging for the very same reasons, even for in vitro experiments. Assumptions, such as the uniformity of the distribution of radionuclides in the culture medium, are commonly made, which could have a profound impact on dose calculations. In this study we measured the spatial distribution of α‐emitting 212Pb coupled to an anti‐VCAM‐1 antibody (212Pb‐αVCAM‐1) and its evolution over time in the context of in vitro irradiations. Methods: Two experimental setups were implemented without cells to measure α‐particle count rates and energy spectra in culture medium containing 15 kBq of 212Pb‐α‐VCAM‐1. Silicon detectors were placed above and below cell culture dishes for 20 h. One of the dishes had a 2.5‐µm‐thick mylar‐base allowing easy detection of the α‐particles. Monte Carlo simulations were performed to analyze experimental spectra. Experimental setups were modeled and α‐energy spectra were simulated in the silicon detectors for different decay positions in the culture medium. Simulated spectra were then used to deconvolute experimental spectra to determine the spatial distribution of 212Pb‐αVCAM‐1 in the medium. This distribution was finally used to calculate the dose deposition in cell culture experiments. Results: Experimental count rates and energy spectra showed differences in measurements taken at the top and the bottom of dishes and temporal variations that did not follow 212Pb decay. The radionuclide spatial distribution was shown to be composed of a uniform distribution and concentration gradients at the top and the bottom, which were subjected to temporal variations that may be explained by gravity and electrostatic attraction. The absorbed dose in cells calculated from this distribution was compared with the dose expected for a uniform and static distribution and found to be 1.75 times higher, which is highly significant to interpret biological observations. Conclusions: This study demonstrated that accurate dosimetry of α‐emitters requires the experimental determination of radionuclide spatial and temporal distribution and highlighted that in vitro assessment of dose for TAT cannot only rely on a uniform distribution of activity in the culture medium. The reliability and reproducibility of future experiments should benefit from specifically developed dosimetry tools and methods. [ABSTRACT FROM AUTHOR]
Copyright of Medical Physics is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Radionuclide spatial distribution and dose deposition for in vitro assessments of <superscript>212</superscript>Pb‐αVCAM‐1 targeted alpha therapy.
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  Data: <searchLink fieldCode="AR" term="%22Frelin‐Labalme%2C+Anne‐Marie%22">Frelin‐Labalme, Anne‐Marie</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> anne-marie.frelin@ganil.fr</i><br /><searchLink fieldCode="AR" term="%22Roger%2C+Thomas%22">Roger, Thomas</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Falzone%2C+Nadia%22">Falzone, Nadia</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Quan+Lee%2C+Boon%22">Quan Lee, Boon</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sibson%2C+Nicola+R%2E%22">Sibson, Nicola R.</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Vallis%2C+Katherine+A%2E%22">Vallis, Katherine A.</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bernaudin%2C+Myriam%22">Bernaudin, Myriam</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Valable%2C+Samuel%22">Valable, Samuel</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Corroyer‐Dulmont%2C+Aurélien%22">Corroyer‐Dulmont, Aurélien</searchLink><relatesTo>2,3</relatesTo> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Medical+Physics%22">Medical Physics</searchLink>. Mar2020, Vol. 47 Issue 3, p1317-1326. 10p.
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  Data: <searchLink fieldCode="DE" term="%22Monte+Carlo+method%22">Monte Carlo method</searchLink><br /><searchLink fieldCode="DE" term="%22Spatial+distribution+%28Quantum+optics%29%22">Spatial distribution (Quantum optics)</searchLink><br /><searchLink fieldCode="DE" term="%22Radioisotopes%22">Radioisotopes</searchLink><br /><searchLink fieldCode="DE" term="%22Silicon+detectors%22">Silicon detectors</searchLink><br /><searchLink fieldCode="DE" term="%22Alpha+rhythm%22">Alpha rhythm</searchLink><br /><searchLink fieldCode="DE" term="%22Absorbed+dose%22">Absorbed dose</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+culture%22">Cell culture</searchLink><br /><searchLink fieldCode="DE" term="%22Energy+transfer%22">Energy transfer</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: Purpose: Targeted alpha therapy (TAT) takes advantage of the short‐range and high‐linear energy transfer of α‐particles and is increasingly used, especially for the treatment of metastatic lesions. Nevertheless, dosimetry of α‐emitters is challenging for the very same reasons, even for in vitro experiments. Assumptions, such as the uniformity of the distribution of radionuclides in the culture medium, are commonly made, which could have a profound impact on dose calculations. In this study we measured the spatial distribution of α‐emitting 212Pb coupled to an anti‐VCAM‐1 antibody (212Pb‐αVCAM‐1) and its evolution over time in the context of in vitro irradiations. Methods: Two experimental setups were implemented without cells to measure α‐particle count rates and energy spectra in culture medium containing 15 kBq of 212Pb‐α‐VCAM‐1. Silicon detectors were placed above and below cell culture dishes for 20 h. One of the dishes had a 2.5‐µm‐thick mylar‐base allowing easy detection of the α‐particles. Monte Carlo simulations were performed to analyze experimental spectra. Experimental setups were modeled and α‐energy spectra were simulated in the silicon detectors for different decay positions in the culture medium. Simulated spectra were then used to deconvolute experimental spectra to determine the spatial distribution of 212Pb‐αVCAM‐1 in the medium. This distribution was finally used to calculate the dose deposition in cell culture experiments. Results: Experimental count rates and energy spectra showed differences in measurements taken at the top and the bottom of dishes and temporal variations that did not follow 212Pb decay. The radionuclide spatial distribution was shown to be composed of a uniform distribution and concentration gradients at the top and the bottom, which were subjected to temporal variations that may be explained by gravity and electrostatic attraction. The absorbed dose in cells calculated from this distribution was compared with the dose expected for a uniform and static distribution and found to be 1.75 times higher, which is highly significant to interpret biological observations. Conclusions: This study demonstrated that accurate dosimetry of α‐emitters requires the experimental determination of radionuclide spatial and temporal distribution and highlighted that in vitro assessment of dose for TAT cannot only rely on a uniform distribution of activity in the culture medium. The reliability and reproducibility of future experiments should benefit from specifically developed dosimetry tools and methods. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
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  Data: <i>Copyright of Medical Physics is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1002/mp.13969
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        Text: English
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      – SubjectFull: Monte Carlo method
        Type: general
      – SubjectFull: Spatial distribution (Quantum optics)
        Type: general
      – SubjectFull: Radioisotopes
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      – SubjectFull: Silicon detectors
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      – SubjectFull: Alpha rhythm
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      – SubjectFull: Absorbed dose
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      – SubjectFull: Cell culture
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      – SubjectFull: Energy transfer
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      – TitleFull: Radionuclide spatial distribution and dose deposition for in vitro assessments of 212Pb‐αVCAM‐1 targeted alpha therapy.
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              Text: Mar2020
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