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J Nucl Med. 2017 Jan;58(1):81-84. doi: 10.2967/jnumed.116.181800. Epub 2016 Sep 22.

68Ga-PSMA-11 PET Imaging of Response to Androgen Receptor Inhibition: First Human Experience.

Author information

1
Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California michael.evans@ucsf.edu.
2
Department of Radiology, San Francisco VA Medical Center, San Francisco, California.
3
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
4
Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California.
5
Department of Radiology, Mayo Clinic, Rochester, Minnesota.
6
Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany.
7
Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California; and.
8
Department of Urology, University of California, San Francisco, San Francisco, California.

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 LNCaP-AR 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.

KEYWORDS:

PET; PSMA PET; androgen receptor; oncology: GU; prostate cancer

PMID:
27660139
PMCID:
PMC5209643
DOI:
10.2967/jnumed.116.181800
[Indexed for MEDLINE]
Free PMC Article

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