Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Quantitative In Vivo Imaging of the Androgen Receptor Axis Reveals Degree of Prostate Cancer Radiotherapy Response

Storey, Claire M ; Altai, Mohamed LU ; Bicak, Mesude ; Veach, Darren R ; Lueckerath, Katharina ; Adrian, Gabriel LU orcid ; McDevitt, Michael R ; Kalidindi, Teja ; Park, Julie E and Herrmann, Ken , et al. (2023) In Molecular cancer research : MCR 21(4). p.1-9
Abstract

Non-invasive biomarkers for androgen receptor (AR) pathway activation are urgently needed to better monitor patient response to prostate cancer (PCa) therapies. AR is a critical driver and mediator of resistance of PCa but currently available non-invasive PCa biomarkers to monitor AR activity are discordant with downstream AR pathway activity. External beam radiotherapy (EBRT) remains a common treatment for all stages of PCa, and DNA damage induced by EBRT upregulates AR pathway activity to promote therapeutic resistance. [89Zr]11B6-PET is a novel modality targeting prostate-specific protein human kallikrein 2 (hK2), which is a surrogate biomarker for AR activity. Here, we studied if [&sup89;Zr]11B6-PET can accurately assess... (More)

Non-invasive biomarkers for androgen receptor (AR) pathway activation are urgently needed to better monitor patient response to prostate cancer (PCa) therapies. AR is a critical driver and mediator of resistance of PCa but currently available non-invasive PCa biomarkers to monitor AR activity are discordant with downstream AR pathway activity. External beam radiotherapy (EBRT) remains a common treatment for all stages of PCa, and DNA damage induced by EBRT upregulates AR pathway activity to promote therapeutic resistance. [89Zr]11B6-PET is a novel modality targeting prostate-specific protein human kallikrein 2 (hK2), which is a surrogate biomarker for AR activity. Here, we studied if [&sup89;Zr]11B6-PET can accurately assess EBRT-induced AR activity. Genetic and human PCa mouse models received EBRT (2-50 Gy) and treatment response was monitored by [89Zr]11B6-PET/CT. Radiotracer uptake and expression of AR and AR target genes was quantified in resected tissue. EBRT increased AR pathway activity and [&sup89;Zr]11B6 uptake in LNCaP-AR and 22RV1 tumors. EBRT increased prostate-specific [&sup89;Zr]11B6 uptake in PCa-bearing mice (Hi-Myc x Pb_KLK2) with no significant changes in uptake in healthy (Pb_KLK2) mice, and this correlated with hK2 protein levels. Implications: hK2 expression in PCa tissue is a proxy of EBRT-induced AR activity that can non-invasively be detected using [&sup89;Zr]11B6-PET; further clinical evaluation of hK2-PET for monitoring response and development of resistance to EBRT in real time is warranted.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular cancer research : MCR
volume
21
issue
4
pages
1 - 9
publisher
American Association for Cancer Research
external identifiers
  • pmid:36608299
  • scopus:85151575199
ISSN
1557-3125
DOI
10.1158/1541-7786.MCR-22-0736
language
English
LU publication?
yes
id
2ba118c6-3324-421a-b2fa-30f9413f7537
date added to LUP
2023-02-07 15:58:58
date last changed
2024-06-15 01:24:15
@article{2ba118c6-3324-421a-b2fa-30f9413f7537,
  abstract     = {{<p>Non-invasive biomarkers for androgen receptor (AR) pathway activation are urgently needed to better monitor patient response to prostate cancer (PCa) therapies. AR is a critical driver and mediator of resistance of PCa but currently available non-invasive PCa biomarkers to monitor AR activity are discordant with downstream AR pathway activity. External beam radiotherapy (EBRT) remains a common treatment for all stages of PCa, and DNA damage induced by EBRT upregulates AR pathway activity to promote therapeutic resistance. [89Zr]11B6-PET is a novel modality targeting prostate-specific protein human kallikrein 2 (hK2), which is a surrogate biomarker for AR activity. Here, we studied if [&amp;sup89;Zr]11B6-PET can accurately assess EBRT-induced AR activity. Genetic and human PCa mouse models received EBRT (2-50 Gy) and treatment response was monitored by [89Zr]11B6-PET/CT. Radiotracer uptake and expression of AR and AR target genes was quantified in resected tissue. EBRT increased AR pathway activity and [&amp;sup89;Zr]11B6 uptake in LNCaP-AR and 22RV1 tumors. EBRT increased prostate-specific [&amp;sup89;Zr]11B6 uptake in PCa-bearing mice (Hi-Myc x Pb_KLK2) with no significant changes in uptake in healthy (Pb_KLK2) mice, and this correlated with hK2 protein levels. Implications: hK2 expression in PCa tissue is a proxy of EBRT-induced AR activity that can non-invasively be detected using [&amp;sup89;Zr]11B6-PET; further clinical evaluation of hK2-PET for monitoring response and development of resistance to EBRT in real time is warranted.</p>}},
  author       = {{Storey, Claire M and Altai, Mohamed and Bicak, Mesude and Veach, Darren R and Lueckerath, Katharina and Adrian, Gabriel and McDevitt, Michael R and Kalidindi, Teja and Park, Julie E and Herrmann, Ken and Abou, Diane and Zedan, Wahed and Peekhaus, Norbert and Klein, Robert J and Damoiseaux, Robert and Larson, Steven M and Lilja, Hans and Thorek, Daniel and Ulmert, David}},
  issn         = {{1557-3125}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{4}},
  pages        = {{1--9}},
  publisher    = {{American Association for Cancer Research}},
  series       = {{Molecular cancer research : MCR}},
  title        = {{Quantitative In Vivo Imaging of the Androgen Receptor Axis Reveals Degree of Prostate Cancer Radiotherapy Response}},
  url          = {{http://dx.doi.org/10.1158/1541-7786.MCR-22-0736}},
  doi          = {{10.1158/1541-7786.MCR-22-0736}},
  volume       = {{21}},
  year         = {{2023}},
}