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Co-injection of anti-HER2 antibody Trastuzumab does not increase efficacy of [177Lu]Lu-PSMA-617 therapy in an animal model of prostate cancer

Abouzayed, Ayman ; Zedan, Wahed LU ; Altai, Mohamed LU ; Strand, Joanna LU and Örbom, Anders LU (2023) In American journal of nuclear medicine and molecular imaging 13(3). p.107-117
Abstract

One novel option for treating metastatic castration resistant prostate cancer is radionuclide therapy targeting prostate-specific membrane antigen (PSMA), e.g. [177Lu]Lu-PSMA-617. Overexpression of HER2 has been found in 80% of metastatic cases of prostate cancer. Previous research showed that HER2 is elevated post irradiation in PC-3 prostate cancer cells. Co-treating with anti-HER2 antibody Trastuzumab gave less proliferation of irradiated tumor cells in vitro, and when using radionuclide therapy, also in vivo. The aim of this study is to determine whether the same holds true in PSMA-expressing PC-3 PIP cells using [177Lu]Lu-PSMA-617 radionuclide therapy. PC-3 PIP and 22Rv1 prostate cancer cells were tested in vitro, treated with 6 Gy... (More)

One novel option for treating metastatic castration resistant prostate cancer is radionuclide therapy targeting prostate-specific membrane antigen (PSMA), e.g. [177Lu]Lu-PSMA-617. Overexpression of HER2 has been found in 80% of metastatic cases of prostate cancer. Previous research showed that HER2 is elevated post irradiation in PC-3 prostate cancer cells. Co-treating with anti-HER2 antibody Trastuzumab gave less proliferation of irradiated tumor cells in vitro, and when using radionuclide therapy, also in vivo. The aim of this study is to determine whether the same holds true in PSMA-expressing PC-3 PIP cells using [177Lu]Lu-PSMA-617 radionuclide therapy. PC-3 PIP and 22Rv1 prostate cancer cells were tested in vitro, treated with 6 Gy of x-rays with or without Trastuzumab incubation. We measured uptake of HER2-targeting affibody [68Ga]Ga-ABY-025 and cell survival, e.g. using the WST-1 assay. Three groups (n=10 each) of male nude Balb/c mice were inoculated with PC-3 PIP xenograft tumors and treated with just [177Lu]Lu-PSMA-617 (20 MBq), [177Lu]Lu-PSMA-617 (20 MBq) and Trastuzumab (4 × 5 mg/kg), or left untreated. Tumor sizes and animal survival was observed. In vitro, x-ray irradiation did reduce survival in 22Rv1 but not PC-3 PIP cells, and there was no significant effect of Trastuzumab treatment. Cells expressed HER2 but not significantly elevated post irradiation. In vivo, mice co-treated with Trastuzumab had significantly longer survival than untreated mice, but not than only [177Lu]Lu-PSMA-617. Staining of tumor sections showed similar HER2 and PSMA expression across groups. In conclusion, these results give no support for any benefit from co-treatment with anti-HER2 antibody for PSMA-targeted radioligand therapy.

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Contribution to journal
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published
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in
American journal of nuclear medicine and molecular imaging
volume
13
issue
3
pages
107 - 117
publisher
e-Century Publishing
external identifiers
  • pmid:37457328
ISSN
2160-8407
language
English
LU publication?
yes
additional info
AJNMMI Copyright © 2023.
id
d5435e49-2d4b-4a3f-8aab-f78b8b38cecd
alternative location
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349288/
date added to LUP
2023-07-18 13:15:45
date last changed
2023-07-24 11:08:47
@article{d5435e49-2d4b-4a3f-8aab-f78b8b38cecd,
  abstract     = {{<p>One novel option for treating metastatic castration resistant prostate cancer is radionuclide therapy targeting prostate-specific membrane antigen (PSMA), e.g. [177Lu]Lu-PSMA-617. Overexpression of HER2 has been found in 80% of metastatic cases of prostate cancer. Previous research showed that HER2 is elevated post irradiation in PC-3 prostate cancer cells. Co-treating with anti-HER2 antibody Trastuzumab gave less proliferation of irradiated tumor cells in vitro, and when using radionuclide therapy, also in vivo. The aim of this study is to determine whether the same holds true in PSMA-expressing PC-3 PIP cells using [177Lu]Lu-PSMA-617 radionuclide therapy. PC-3 PIP and 22Rv1 prostate cancer cells were tested in vitro, treated with 6 Gy of x-rays with or without Trastuzumab incubation. We measured uptake of HER2-targeting affibody [68Ga]Ga-ABY-025 and cell survival, e.g. using the WST-1 assay. Three groups (n=10 each) of male nude Balb/c mice were inoculated with PC-3 PIP xenograft tumors and treated with just [177Lu]Lu-PSMA-617 (20 MBq), [177Lu]Lu-PSMA-617 (20 MBq) and Trastuzumab (4 × 5 mg/kg), or left untreated. Tumor sizes and animal survival was observed. In vitro, x-ray irradiation did reduce survival in 22Rv1 but not PC-3 PIP cells, and there was no significant effect of Trastuzumab treatment. Cells expressed HER2 but not significantly elevated post irradiation. In vivo, mice co-treated with Trastuzumab had significantly longer survival than untreated mice, but not than only [177Lu]Lu-PSMA-617. Staining of tumor sections showed similar HER2 and PSMA expression across groups. In conclusion, these results give no support for any benefit from co-treatment with anti-HER2 antibody for PSMA-targeted radioligand therapy.</p>}},
  author       = {{Abouzayed, Ayman and Zedan, Wahed and Altai, Mohamed and Strand, Joanna and Örbom, Anders}},
  issn         = {{2160-8407}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{3}},
  pages        = {{107--117}},
  publisher    = {{e-Century Publishing}},
  series       = {{American journal of nuclear medicine and molecular imaging}},
  title        = {{Co-injection of anti-HER2 antibody Trastuzumab does not increase efficacy of [177Lu]Lu-PSMA-617 therapy in an animal model of prostate cancer}},
  url          = {{https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349288/}},
  volume       = {{13}},
  year         = {{2023}},
}