Role of Androgen Receptor Blockade on PSMA Expression Using ⁶⁸Ga-PSMA-11 PET/CT Imaging in Patients with Metastatic Prostate Cancer

• Areas of Interest: Theragnostics

Background: There is evidence to suggest that ⁶⁸Ga-PSMA PET/CT imaging is sensitive to effects of androgen deprivation therapy (ADT). However, there is conflicting clinical support in the literature whether androgen receptor (AR) blockade in the setting of castrate resistance could enhance lesion detection by ⁶⁸Ga-PSMA PET/CT. We present preliminary results of a prospective investigator-initiated trial in patients with metastatic prostate cancer (mPC) that seeks to elucidate the effect of androgen blockade by enzalutamide on the diagnostic sensitivity of ⁶⁸Ga-PSMA PET/CT.

Methods: mPC patients with demonstrated castrate resistance to standard ADT, rising PSA levels and were suitable for standard second-line treatment with an AR blocker were considered eligible. Enrolled patients underwent two ⁶⁸Ga-PSMA-11 PET/CT scans prepared from an investigational “cold kit” provided by Telix Pharmaceuticals; the first scan occurred 28 days prior to enzalutamide treatment and the second scan 14 to 28 days after commencing enzalutamide. Lesions were segmented using a thresholding method. A 3-cm SUV sphere was placed in the center of the liver's right lobe in the preenzalutamide scan to extract the liver mean and standard deviation (SD) and a SUV threshold of liver mean +2 SD was set for each patient. For a patient with only metastatic lung lesions, a method of 70% thresholding at the SUVmax was applied as the liver background SUV was higher than SUV of all lung lesions.

Results: To date, 10 patients have been enrolled. Imaging data of three patients was excluded for analysis: the first patient due to medication error (40 mg rather than 160 mg); the second patient did not complete second scan (intercurrent medical illness); and the imaging data of the third patient was not available for analysis (image reconstruction error). One patient had no detectable lesions in both scans. For the remaining 6 patients, a median 14% (interquartile range [IQR]: –14 to 17%) decrease in total-body SUVmax was recorded from pre- to postenzalutamide scans. PSMA response heterogeneity was noted, with decreasing SUVmax in 67% (4/6) patients and marked increase in 33% (2/6) patients (+23 and +38%, respectively). Similar pattern was recorded for total-body SUVmean with a median 8% ([IQR]: –2 to 21%) reduction.

Conclusion: Based on the patients enrolled to date, the effect of AR blockade in patients with castrate resistant mPC on lesion detection by ⁶⁸Ga-PSMA PET/CT is heterogeneous. Upregulation of PSMA is not definitive in this group of patients and downregulation may occur. We are currently increasing enrolment of patients to better clarify the effect of AR blockade on PSMA upregulation.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
10 May 2022