68Ga-PSMA-11 PET imaging of response to androgen receptor inhibition: First human experience

Thomas A. Hope, Charles Truillet, Eric C. Ehman, Ali Afshar-Oromieh, Rahul Aggarwal, Charles J. Ryan, Peter R. Carroll, Eric J. Small, Michael J. Evans

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

The purpose of this work was to evaluate the effect of androgen receptor (AR) inhibition on prostate-specific membrane antigen (PSMA) uptake imaged using 68Ga-PSMA-11 PET in a mouse xenograft model and in a patient with castration-sensitive prostate cancer. Methods: We imaged 3 groups of 4 mice bearing LNCaPAR xenografts before and 7 d after treatment with ARN-509, orchiectomy, or control vehicle. Additionally, we imaged one patient with castration-sensitive prostate cancer before and 4 wk after treatment with androgen deprivation therapy (ADT). Uptake on pre-and posttreatment imaging was measured and compared. Results: PSMA uptake increased 1.5-to 2.0-fold in the xenograft mouse model after treatment with both orchiectomy and ARN-509 but not with vehicle. Patient imaging demonstrated a 7-fold increase in PSMA uptake after the initiation of ADT. Thirteen of 22 lesions in the imaged patient were visualized on PSMA PET only after treatment with ADT. Conclusion: Inhibition of the AR can increase PSMA expression in prostate cancer metastases and increase the number of lesions visualized using PSMA PET. The effect seen in cell and animal models can be recapitulated in humans. A better understanding of the temporal changes in PSMA expression is needed to leverage this effect for both improved diagnosis and improved therapy.

Original languageEnglish (US)
Pages (from-to)81-84
Number of pages4
JournalJournal of Nuclear Medicine
Volume58
Issue number1
DOIs
StatePublished - Jan 1 2017

Keywords

  • Androgen receptor
  • Oncology: GU
  • PET
  • PSMA PET
  • Prostate cancer

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    Hope, T. A., Truillet, C., Ehman, E. C., Afshar-Oromieh, A., Aggarwal, R., Ryan, C. J., Carroll, P. R., Small, E. J., & Evans, M. J. (2017). 68Ga-PSMA-11 PET imaging of response to androgen receptor inhibition: First human experience. Journal of Nuclear Medicine, 58(1), 81-84. https://doi.org/10.2967/jnumed.116.181800