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

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.

FIGURE 1.

⁶⁸Ga-PSMA-11 PET demonstrates increased PSMA expression in prostate cancer xenografts with inhibition of AR. (A) Ratio of SUV_mean at day 7 to day 0 increased an average of 72% with orchiectomy and 105% with ARN-509 compared with vehicle. (B) Visual assessment of ⁶⁸Ga-PSMA-11 PET demonstrates clear increase in uptake in xenografts in response to ARN-509 (middle row) and orchiectomy (bottom row), compared with controls treated with vehicle (top row). *P = 0.007. **P = 0.013. ID = injected dose; ROI = region of interest; RX = treatment.

FIGURE 2.

(A and B) Coronal maximum-intensity projections of patient with castration-sensitive metastatic prostate cancer imaged using ⁶⁸Ga-PSMA-11 before ADT (A) and after ADT (B) demonstrate marked increase in uptake in lesions. (C) Each visualized lesion demonstrated increased uptake, averaging more than 7 times the initial uptake. (D and E) Numerous lesions (13 of 22) were visualized only on posttreatment imaging, as exemplified by the upper thoracic osseous metastasis seen on these axial PET images. (F and G) Other lesions increased in size and had increased uptake on posttreatment imaging, as exemplified by the lesion seen on these axial PET images.

FIGURE 3.

Examples of lesions seen only on post-ADT PSMA PET. (A) Pretreatment PET image demonstrates single lesion (circled) in right acetabulum. (B) Additional non–PSMA-avid right acetabular lesion (arrow) is seen just lateral to larger lesion on MR image of same location. (C) On post-ADT PET image, numerous additional lesions are seen, including adjacent acetabular lesion (arrow). (D) This lesion (arrow) is again demonstrated on enhanced T1-weighted MR image.