TY  - JOUR
AU  - Storey, Claire M
AU  - Altai, Mohamed
AU  - Bicak, Mesude
AU  - Veach, Darren R
AU  - Lueckerath, Katharina
AU  - Adrian, Gabriel
AU  - McDevitt, Michael R
AU  - Kalidindi, Teja
AU  - Park, Julie E
AU  - Herrmann, Ken
AU  - Abou, Diane
AU  - Zedan, Wahed
AU  - Peekhaus, Norbert
AU  - Klein, Robert J
AU  - Damoiseaux, Robert
AU  - Larson, Steven M
AU  - Lilja, Hans
AU  - Thorek, Daniel
AU  - Ulmert, David
TI  - Quantitative In Vivo Imaging of the Androgen Receptor Axis Reveals Degree of Prostate Cancer Radiotherapy Response.
JO  - Molecular cancer research
VL  - 21
IS  - 4
SN  - 1541-7786
CY  - Philadelphia, Pa.
PB  - AACR
M1  - DKFZ-2023-00039
SP  - 307-315
PY  - 2023
N1  - 2023 Apr 1;21(4):307-315
AB  - 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 [</td><td width="150">
AB  - 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 [</td><td width="150">
AB  - sup89;Zr]11B6 uptake in LNCaP-AR and 22RV1 tumors. EBRT increased prostate-specific [</td><td width="150">
AB  - 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 [</td><td width="150">
AB  - sup89;Zr]11B6-PET; further clinical evaluation of hK2-PET for monitoring response and development of resistance to EBRT in real time is warranted.
LB  - PUB:(DE-HGF)16
C6  - pmid:36608299
DO  - DOI:10.1158/1541-7786.MCR-22-0736
UR  - https://inrepo02.dkfz.de/record/186670
ER  -