To evaluate the effect of androgen receptor (AR) inhibition on Prostate Specific Membrane Antigen (PSMA) uptake imaged using (68)Ga-PSMA-11 Positron Emission Tomography (PET) in a mouse xenograft model and in a patient with castration sensitive prostate cancer.
We imaged three groups of four mice bearing LNCaP-AR xenografts before and seven days after treatment with ARN-509, orchiectomy and control vehicle. Additionally, we imaged one patient with castration sensitive prostate cancer before and four weeks after treatment with androgen deprivation therapy (ADT). Uptake on pre- and post-treatment imaging was measured and compared.
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 seven-fold increase in PSMA uptake after the initiation of ADT. 13 of 22 lesions in the imaged patient were only visualized on PSMA PET after treatment with ADT.
Inhibition of the AR can increase PSMA expression in prostate cancer metastases and increase the number of lesions visualized using PSMA PET. The effects seen in cell and animal models can be recapitulated in humans. Further work needs to be done to better understand temporal changes of PSMA expression in order to leverage this effect for both improved diagnosis and therapy.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2016 Sep 22 [Epub ahead of print]
Thomas A Hope, Charles C Truillet, Eric C Ehman, Ali Afshar-Oromieh, Rahul Aggarwal, Charles J Ryan, Peter R Carroll, Eric J Small, Michael John Evans
University of California, San Francisco, United States;, Mayo Clinic;, University Hospital of Heidelberg/Germany, Germany;, University of California San Francisco, United States.