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 Lueckerath, 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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review


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.

Sidor (från-till)OF1-OF9
TidskriftMolecular cancer research : MCR
StatusPublished - 2023 apr. 1

Ämnesklassifikation (UKÄ)

  • Cancer och onkologi
  • Radiologi och bildbehandling


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