Advanced

High resolution digital autoradiographic and dosimetric analysis of heterogeneous radioactivity distribution in xenografted prostate tumors

Vilhelmsson Timmermand, Oskar LU ; Nilsson, Jenny LU ; Strand, Sven Erik LU and Elgqvist, Jörgen LU (2016) In Medical Physics 43(12). p.6632-6643
Abstract

Purpose: The frst main aim of this study was to illustrate the absorbed dose rate distribution from 177Lu in sections of xenografted prostate cancer (PCa) tumors using high resolution digital autoradiography (DAR) and compare it with hypothetical identical radioactivity distributions of 90Y or 7 MeV alpha-particles. Three dosimetry models based on either dose point kernels or Monte Carlo simulations were used and evaluated. The second and overlapping aim, was to perform DAR imaging and dosimetric analysis of the distribution of radioactivity, and hence the absorbed dose rate, in tumor sections at an early time point after injection during radioimmunotherapy using 177Lu-h11B6, directed against the human kallikrein 2... (More)

Purpose: The frst main aim of this study was to illustrate the absorbed dose rate distribution from 177Lu in sections of xenografted prostate cancer (PCa) tumors using high resolution digital autoradiography (DAR) and compare it with hypothetical identical radioactivity distributions of 90Y or 7 MeV alpha-particles. Three dosimetry models based on either dose point kernels or Monte Carlo simulations were used and evaluated. The second and overlapping aim, was to perform DAR imaging and dosimetric analysis of the distribution of radioactivity, and hence the absorbed dose rate, in tumor sections at an early time point after injection during radioimmunotherapy using 177Lu-h11B6, directed against the human kallikrein 2 antigen. Methods: Male immunodefcient BALB/c nude mice, aged 6-8 w, were inoculated by subcutaneous injection of ∼107 LNCaP cells in a 200 μl suspension of a 1:1 mixture of medium and Matrigel. The antibody h11B6 was conjugated with the chelator CHX-A''-DTPA after which conjugated h11B6 was mixed with 177LuCl3. The incubation was performed at room temperature for 2 h, after which the labeling was terminated and the solution was purifed on a NAP-5 column. About 20 MBq 177Lu-h11B6 was injected intravenously in the tail vein. At approximately 10 h postinjection (hpi), the mice were sacrifced and one tumor was collected from each of the fve animals and cryosectioned into 10 μ m thick slices. The tumor slices were measured and imaged using the DAR MicroImager system and the M3Vision software. Then the absorbed dose rate was calculated using a dose point kernel generated with the Monte Carlo code Gate v7.0. Results: The DAR system produced high resolution images of the radioactivity distribution, close to the resolution of single PCa cells. The DAR images revealed a pronounced heterogeneous radioactivity distribution, i.e., count rate per area, in the tumors, indicated by the normalized intensity variations along cross sections as mean ± SD: 0.15±0.15, 0.20±0.18, 0.12±0.17, 0.15±0.16, and 0.23±0.22, for each tumor section, respectively. The absorbed dose rate distribution for 177Lu at the time of dissection 10 hpi showed a maximum value of 2.9±0.4 Gy/h (mean ± SD), compared to 6.0±0.9 and 159±25 Gy/h for the hypothetical 90Y and 7 MeV alpha-particle cases assuming the same count rate densities. Mean absorbed dose rate values were 0.13, 0.53, and 6.43 Gy/h for 177Lu, 90Y, and alpha-particles, respectively. Conclusions: The initial uptake of 177Lu-h11B6 produces a high absorbed dose rate, which is important for a successful therapeutic outcome. The hypothetical 90Y case indicates a less heterogeneous absorbed dose rate distribution and a higher mean absorbed dose rate compared to 177Lu, although with a potentially increased irradiation of surrounding healthy tissue. The hypothetical alpha-particle case indicates the possibility of a higher maximum absorbed dose rate, although with a more heterogeneous absorbed dose rate distribution.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Lu, Y, alpha-particles, digital autoradiography, dosimetry, prostate cancer
in
Medical Physics
volume
43
issue
12
pages
12 pages
publisher
American Association of Physicists in Medicine
external identifiers
  • scopus:84999271396
  • wos:000390237200041
ISSN
0094-2405
DOI
10.1118/1.4967877
language
English
LU publication?
yes
id
734c7ace-cace-44ae-81ea-f3a6e8c96cdf
date added to LUP
2016-12-16 12:52:09
date last changed
2017-09-18 11:31:42
@article{734c7ace-cace-44ae-81ea-f3a6e8c96cdf,
  abstract     = {<p>Purpose: The frst main aim of this study was to illustrate the absorbed dose rate distribution from <sup>177</sup>Lu in sections of xenografted prostate cancer (PCa) tumors using high resolution digital autoradiography (DAR) and compare it with hypothetical identical radioactivity distributions of 90Y or 7 MeV alpha-particles. Three dosimetry models based on either dose point kernels or Monte Carlo simulations were used and evaluated. The second and overlapping aim, was to perform DAR imaging and dosimetric analysis of the distribution of radioactivity, and hence the absorbed dose rate, in tumor sections at an early time point after injection during radioimmunotherapy using <sup>177</sup>Lu-h11B6, directed against the human kallikrein 2 antigen. Methods: Male immunodefcient BALB/c nude mice, aged 6-8 w, were inoculated by subcutaneous injection of ∼10<sup>7</sup> LNCaP cells in a 200 μl suspension of a 1:1 mixture of medium and Matrigel. The antibody h11B6 was conjugated with the chelator CHX-A''-DTPA after which conjugated h11B6 was mixed with <sup>177</sup>LuCl3. The incubation was performed at room temperature for 2 h, after which the labeling was terminated and the solution was purifed on a NAP-5 column. About 20 MBq <sup>177</sup>Lu-h11B6 was injected intravenously in the tail vein. At approximately 10 h postinjection (hpi), the mice were sacrifced and one tumor was collected from each of the fve animals and cryosectioned into 10 μ m thick slices. The tumor slices were measured and imaged using the DAR MicroImager system and the M3Vision software. Then the absorbed dose rate was calculated using a dose point kernel generated with the Monte Carlo code Gate v7.0. Results: The DAR system produced high resolution images of the radioactivity distribution, close to the resolution of single PCa cells. The DAR images revealed a pronounced heterogeneous radioactivity distribution, i.e., count rate per area, in the tumors, indicated by the normalized intensity variations along cross sections as mean ± SD: 0.15±0.15, 0.20±0.18, 0.12±0.17, 0.15±0.16, and 0.23±0.22, for each tumor section, respectively. The absorbed dose rate distribution for 177Lu at the time of dissection 10 hpi showed a maximum value of 2.9±0.4 Gy/h (mean ± SD), compared to 6.0±0.9 and 159±25 Gy/h for the hypothetical 90Y and 7 MeV alpha-particle cases assuming the same count rate densities. Mean absorbed dose rate values were 0.13, 0.53, and 6.43 Gy/h for <sup>177</sup>Lu, 90Y, and alpha-particles, respectively. Conclusions: The initial uptake of <sup>177</sup>Lu-h11B6 produces a high absorbed dose rate, which is important for a successful therapeutic outcome. The hypothetical 90Y case indicates a less heterogeneous absorbed dose rate distribution and a higher mean absorbed dose rate compared to <sup>177</sup>Lu, although with a potentially increased irradiation of surrounding healthy tissue. The hypothetical alpha-particle case indicates the possibility of a higher maximum absorbed dose rate, although with a more heterogeneous absorbed dose rate distribution.</p>},
  author       = {Vilhelmsson Timmermand, Oskar and Nilsson, Jenny and Strand, Sven Erik and Elgqvist, Jörgen},
  issn         = {0094-2405},
  keyword      = {Lu,Y,alpha-particles,digital autoradiography,dosimetry,prostate cancer},
  language     = {eng},
  month        = {12},
  number       = {12},
  pages        = {6632--6643},
  publisher    = {American Association of Physicists in Medicine},
  series       = {Medical Physics},
  title        = {High resolution digital autoradiographic and dosimetric analysis of heterogeneous radioactivity distribution in xenografted prostate tumors},
  url          = {http://dx.doi.org/10.1118/1.4967877},
  volume       = {43},
  year         = {2016},
}