TY - JOUR
T1 - Quantitative In Vivo Imaging of the Androgen Receptor Axis Reveals Degree of Prostate Cancer Radiotherapy Response
AU - Storey, Claire M.
AU - Altai, Mohamed
AU - Bicak, Mesude
AU - Veach, Darren R.
AU - Lückerath, 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
N1 - Publisher Copyright:
© 2023 American Association for Cancer Research.
PY - 2023/4/1
Y1 - 2023/4/1
N2 - Noninvasive biomarkers for androgen receptor (AR) pathway activation are urgently needed to better monitor patient response to prostate cancer therapies. AR is a critical driver and mediator of resistance of prostate cancer but currently available noninvasive prostate cancer biomarkers to monitor AR activity are discordant with downstream AR pathway activity. External beam radiotherapy (EBRT) remains a common treatment for all stages of prostate cancer, 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 whether [89Zr]11B6-PET can accurately assess EBRT-induced AR activity. Genetic and human prostate cancer 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 [89Zr]11B6 uptake in LNCaP-AR and 22RV1 tumors. EBRT increased prostate-specific [89Zr]11B6 uptake in prostate cancer–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.
AB - Noninvasive biomarkers for androgen receptor (AR) pathway activation are urgently needed to better monitor patient response to prostate cancer therapies. AR is a critical driver and mediator of resistance of prostate cancer but currently available noninvasive prostate cancer biomarkers to monitor AR activity are discordant with downstream AR pathway activity. External beam radiotherapy (EBRT) remains a common treatment for all stages of prostate cancer, 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 whether [89Zr]11B6-PET can accurately assess EBRT-induced AR activity. Genetic and human prostate cancer 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 [89Zr]11B6 uptake in LNCaP-AR and 22RV1 tumors. EBRT increased prostate-specific [89Zr]11B6 uptake in prostate cancer–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.
UR - http://www.scopus.com/inward/record.url?scp=85151575199&partnerID=8YFLogxK
U2 - 10.1158/1541-7786.MCR-22-0736
DO - 10.1158/1541-7786.MCR-22-0736
M3 - Article
C2 - 36608299
AN - SCOPUS:85151575199
SN - 1541-7786
VL - 21
SP - 307
EP - 315
JO - Molecular Cancer Research
JF - Molecular Cancer Research
IS - 4
ER -