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

Claire M. Storey, Mohamed Altai, Mesude Bicak, Darren R. Veach, Katharina Lückerath, Gabriel Adrian, Michael R. McDevitt, Teja Kalidindi, Julie E. Park, Ken Herrmann, Diane Abou, Wahed Zedan, Norbert Peekhaus, Robert J. Klein, Robert Damoiseaux, Steven M. Larson, Hans Lilja, Daniel Thorek, David Ulmert

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish
Pages (from-to)307-315
Number of pages9
JournalMolecular Cancer Research
Issue number4
StatePublished - Apr 1 2023


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