Quantitative in vivo imaging of the androgen receptor axis reveals degree of prostate cancer radiotherapy response Journal Article
| Authors: | Storey, C. M.; Altai, M.; Bicak, M.; Veach, D. R.; Lückerath, K.; Adrian, G.; McDevitt, M. R.; Kalidindi, T.; Park, J. E.; Herrmann, K.; Abou, D.; Zedan, W.; Peekhaus, N.; Klein, R. J.; Damoiseaux, R.; Larson, S. M.; Lilja, H.; Thorek, D.; Ulmert, D. |
| Article Title: | Quantitative in vivo imaging of the androgen receptor axis reveals degree of prostate cancer radiotherapy response |
| 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. 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. ©2023 American Association for Cancer Research. |
| Keywords: | genetics; mouse; animal; metabolism; animals; mice; cell line, tumor; diagnostic imaging; prostatic neoplasms; prostate tumor; tumor cell line; androgen receptor; radioisotope; receptors, androgen; radioisotopes; zirconium; zirconium-89; lead; humans; human; male; positron emission tomography-computed tomography; positron emission tomography computed tomography |
| Journal Title: | Molecular Cancer Research |
| Volume: | 21 |
| Issue: | 4 |
| ISSN: | 1541-7786 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2023-04-01 |
| Start Page: | 307 |
| End Page: | 315 |
| Language: | English |
| DOI: | 10.1158/1541-7786.Mcr-22-0736 |
| PUBMED: | 36608299 |
| PROVIDER: | scopus |
| PMCID: | PMC10355285 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- Export Date: 1 May 2023 -- Source: Scopus |
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