Assessing Functional Androgen Receptor Pathway Activity in Response to Radiotherapy Using hK2-targeted PET Imaging

Storey, C. M.; Altai, M.; Bicak, M.; Veach, D. R.; Lueckerath, 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.; Lilija, H.; Thorek, D.; Thorek, D. L.; Ulmert, D.

doi:10.1101/2022.06.23.497290

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bioRxiv · 10.1101/2022.06.23.497290

Assessing Functional Androgen Receptor Pathway Activity in Response to Radiotherapy Using hK2-targeted PET Imaging

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Abstract

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.

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Storey, C. M., Altai, M., Bicak, M., Veach, D. R., Lueckerath, 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., Lilija, H., Thorek, D., Thorek, D. L., Ulmert, D.. 2022-06-26. Assessing Functional Androgen Receptor Pathway Activity in Response to Radiotherapy Using hK2-targeted PET Imaging. https://doi.org/10.1101/2022.06.23.497290

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