%0 Journal Article %A Claire M Storey %A Mohamed Altai %A Mesude Bicak %A Darren R Veach %A Katharina Lückerath %A Gabriel Adrian %A Michael R McDevitt %A Teja Kalidindi %A Julie E Park %A Ken Herrmann %A Diane Abou %A Wahed Zedan %A Norbert Peekhaus %A Robert J Klein %A Robert Damoiseaux %A Steven M Larson %A Hans Lilja %A Daniel Thorek %A David Ulmert %T Assessing Functional Androgen Receptor Pathway Activity in Response to Radiotherapy Using hK2-targeted PET Imaging %D 2022 %R 10.1101/2022.06.23.497290 %J bioRxiv %P 2022.06.23.497290 %X External beam radiotherapy (EBRT) remains a common treatment for all stages of PCa, but DNA damage induced by EBRT upregulates androgen receptor (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 [89Zr]11B6-PET can accurately assess EBRT-induced AR activity. 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 in LNCaP-AR tumors. EBRT increased prostate-specific [89Zr]11B6 uptake and hK2 levels in PCa-bearing mice (Hi-Myc x Pb_KLK2) with no significant changes in uptake in healthy (Pb_KLK2) mice. Thus, [89Zr]11B6-PET specifically detects activation of AR pathway activity after EBRT in PCa. Further clinical evaluation of hK2-PET for monitoring EBRT is warranted.Competing Interest StatementC. Storey is named on a patent in the field of radioimmunotherapy and drug delivery pending, licensed, and with royalties from Radiopharm Theranostics. M. Altai reports grants from Swedish Cancer Foundation, Kamprad Foundation and Lund University, Lundberg Foundation and Bergqvist Foundation; is a consultant for Genagon AB and Pharma15 C-Corp. K. Lueckerath reports personal fees from Sofie Biosciences outside the submitted work. R. Damoiseaux reports a patent for Antibodies pending. S.M. Larson reports grants from NIH during the conduct of the study, and grants from YMABS Therapeutics Inc and royalties from Elucida, SAMOs, and YMABS Therapeutic Inc outside the submitted work; in addition, S.M. Larson has several patents in the field of Radioimmunotherapy and Drug delivery pending, issued, licensed, and with royalties paid from YMABS Therapeutic; a patent for Nanoparticles issued, licensed, and with royalties paid from Elucida Inc; and a patent for radiotracer drugs from SAMOS; and reports consultation regarding drug products with Progenics, Janssen, and Exini (Lantheus) during the conduct of this work and preparation of article. H. Lilja is named on patents for intact PSA assays and a statistical method to detect prostate cancer (4KScore test) that has been commercialized by OPKO Health; receives royalties and has stock in OPKO Health; has been a consultant to Diaprost AB and has stock in Diaprost AB; and has received a speaker's honorarium from Janssen R&D LLC. D.L.J. Thorek reports grants from NIH NCI (R0128335, R0128238, R0128539) during the conduct of the study and is scientific advisor for and has equity in Diaprost AB and Pharma15. D. Ulmert reports grants from Prostate Cancer Foundation, Rosehill Foundation, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Kamprad Foundation, Swedish Research Foundation, Swedish Cancer Foundation, Sanofi Innovation, Janssen R&D LLC, and Department of Defense during the conduct of the study; has several patents in the field of Radioimmunotherapy and Drug delivery pending, issued, licensed, and with royalties paid from YMABS Therapeutic, Radiopharm Theranostics, and Diaprost AB outside the submitted work; is a consultant for Astra Zeneca, Two River, Ferring Ventures, Vida Ventures, Novartis Ventures, Genagon AB, Pharma15 C-Corp, and Diaprost AB. %U https://www.biorxiv.org/content/biorxiv/early/2022/06/26/2022.06.23.497290.full.pdf