Quantitative In Vivo Imaging of the Androgen Receptor Axis Reveals Degree of Prostate Cancer Radiotherapy Response
(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)
- author
- organization
- publishing date
- 2023-04-01
- 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 [&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.</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}}, }