Quantitative<i>In Vivo</i>Imaging of the Androgen Receptor Axis Reveals Degree of Prostate Cancer Radiotherapy Response-Reference-Cited by-同舟云学术

QuantitativeIn VivoImaging of the Androgen Receptor Axis Reveals Degree of Prostate Cancer Radiotherapy Response

Published:2023-01-06 Issue:4 Volume:21 Page:307-315
ISSN:1541-7786
Container-title:Molecular Cancer Research
language:en
Short-container-title:

Author:

Storey Claire M.¹^ORCID,Altai Mohamed²^ORCID,Bicak Mesude³^ORCID,Veach Darren R.⁴^ORCID,Lückerath Katharina⁵^ORCID,Adrian Gabriel²^ORCID,McDevitt Michael R.⁴^ORCID,Kalidindi Teja⁴^ORCID,Park Julie E.¹^ORCID,Herrmann Ken⁵^ORCID,Abou Diane⁶⁷^ORCID,Zedan Wahed²^ORCID,Peekhaus Norbert²^ORCID,Klein Robert J.⁸^ORCID,Damoiseaux Robert¹⁹^ORCID,Larson Steven M.⁴¹⁰^ORCID,Lilja Hans¹¹¹²¹³¹⁴^ORCID,Thorek Daniel⁶⁷¹⁵^ORCID,Ulmert David¹²⁹¹⁶¹⁷¹⁸^ORCID

Affiliation:

1. 1Department of Molecular & Medical Pharmacology, University of California Los Angeles (UCLA), Los Angeles, California.

2. 2Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.

3. 3Hasso Plattner Institute for Digital Health, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.

4. 4Department of Radiology, Memorial Sloan Kettering Cancer Center (MSKCC), New York, New York.

5. 5Department of Nuclear Medicine, University Hospital Essen, University of Duisburg-Essen, DKTK, Essen, Germany.

6. 6Department of Radiology, Washington University School of Medicine, St. Louis, Missouri.

7. 7Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.

8. 8Icahn Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic, Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.

9. 9California NanoSystems Institute, UCLA, Los Angeles, California.

10. 10Department of Radiology, Weill Cornell Medical College, New York, New York.

11. 11Genitourinary Oncology Service, Department of Medicine, MSKCC, New York, New York.

12. 12Urology Service, Department of Surgery, MSKCC, New York, New York.

13. 13Department of Laboratory Medicine, MSKCC, New York, New York.

14. 14Department of Translational Medicine, Lund University, Malmö, Sweden.

15. 15Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, Missouri.

16. 16Department of Urology, Institute of Urologic Oncology, UCLA, Los Angeles, California.

17. 17Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, UCLA, Los Angeles, California.

18. 18Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, California.

Abstract

AbstractNoninvasive 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.Implications: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.

Funder

Jonsson Comprehensive Cancer Center

Cancerfonden

Vetenskapsrådet

Sidney Kimmel Center for Prostate and Urologic Cancers

U.S. Department of Defense

National Cancer Institute

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

Rose Hills Foundation

Memorial Sloan-Kettering Cancer Center

Geoffrey Beene Cancer Research Center

Commonwealth Foundation for Cancer Research Foundation