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Supplementary Figures 1 and 2 from Quantitative In Vivo Imaging of the Androgen Receptor Axis Reveals Degree of Prostate Cancer Radiotherapy Response

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posted on 2023-04-03, 08:41 authored by 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

S1. Hierarchical clustering based on Euclidean distance of RNA-seq data demonstrates separation of EBRT-treated (B1-3) and untreated (C1-3) samples.S2. Multi-dimensional scaling plot of RNA-seq data demonstrates separation of EBRT-treated (B1-3) and untreated (C1-3) samples.

Funding

Jonsson Comprehensive Cancer Center (JCCC)

Cancerfonden (Swedish Cancer Society)

Vetenskapsrådet (VR)

Sidney Kimmel Center for Prostate and Urologic Cancers (Sidney Kimmel Center)

U.S. Department of Defense (DOD)

National Cancer Institute (NCI)

United States Department of Health and Human Services

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Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles (Broad Stem Cell Research Center)

Rose Hills Foundation (RHF)

Memorial Sloan-Kettering Cancer Center (MSK)

Geoffrey Beene Cancer Research Center

Commonwealth Foundation for Cancer Research Foundation

Prostate Cancer Foundation (PCF)

Allmänna Sjukhusets i Malmö Stiftelse för Bekämpande av Cancer (General Hospital of Malmö Foundation for Fighting Cancer)

Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)

Fru Berta Kamprads Stiftelse (Mrs. Berta Kamprad Foundation)

History

ARTICLE ABSTRACT

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. hK2 expression in prostate cancer tissue is a proxy of EBRT-induced AR activity that can noninvasively be detected using [89Zr]11B6-PET; further clinical evaluation of hK2-PET for monitoring response and development of resistance to EBRT in real time is warranted.

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