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@ARTICLE{Storey:186670,
author = {C. M. Storey and M. Altai and M. Bicak and D. R. Veach and
K. Lueckerath$^*$ and G. Adrian and M. R. McDevitt and T.
Kalidindi and J. E. Park and K. Herrmann$^*$ and D. Abou and
W. Zedan and N. Peekhaus and R. J. Klein and R. Damoiseaux
and S. M. Larson and H. Lilja and D. Thorek and D. Ulmert},
title = {{Q}uantitative {I}n {V}ivo {I}maging of the {A}ndrogen
{R}eceptor {A}xis {R}eveals {D}egree of {P}rostate {C}ancer
{R}adiotherapy {R}esponse.},
journal = {Molecular cancer research},
volume = {21},
number = {4},
issn = {1541-7786},
address = {Philadelphia, Pa.},
publisher = {AACR},
reportid = {DKFZ-2023-00039},
pages = {307-315},
year = {2023},
note = {2023 Apr 1;21(4):307-315},
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 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.},
cin = {ED01},
ddc = {610},
cid = {I:(DE-He78)ED01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36608299},
doi = {10.1158/1541-7786.MCR-22-0736},
url = {https://inrepo02.dkfz.de/record/186670},
}