Enhancing PSMA-uptake with androgen deprivation therapy – a new way to detect prostate cancer metastases?

Abstract

Purpose: 68Ga-PSMA PET/CT imaging is a promising modality for the staging of recurrent prostate cancer (PCa). Current evidence suggests limited diagnostic value of the 68Ga-PSMA PET/CT in PSA-levels ≤0.3ng/mL. Experimental data have demonstrated an increase in PSMA-expression in PCa metastases by androgen deprivation in vitro. The aim of the current study was to investigate a possible enhancing effect of PSMA with low-dose androgen deprivation in patients with BCR and low PSA-levels.Materials and Methods:Five patients with PCa and BCR, following radical prostatectomy, underwent 68Ga-PSMA PET/CT. A consecutive 68Ga-PSMA PET/CT was performed 6 to 11 days after injection of 80mg of Degarelix (Firmagon®). We recorded PSA and testosterone serum-levels and changes of PSMA-uptake in 68Ga-PSMA PET/CT images. Results: Median PSA prior 68Ga-PSMA PET/CT was 0.27ng/mL. All patients had a decrease in testosterone serum levels from median 2.95μg/l to 0.16μg/l following Degarelix injection. We observed an increase in the standardized uptake value (SUV) in PSMA-positive lymphogenous and osseous lesions in two patients following androgen deprivation. In another two patients, no PSMA positive signals were detected in either the first or the second scan.Conclusion:Our preliminary results of this feasibility assessment indicate a possible enhancing effect of PSMA-imaging induced by low-dose ADT. Despite several limitations and the small number of patients, this could be a new approach to improve staging by 68Ga-PSMA PET/CT in PCa patients with BCR after primary therapy. Further prospective studies with larger number of patients are needed to validate our findings.

Influence of androgen deprivation therapy on PSMA expression and PSMA-ligand PET imaging of prostate cancer patients

“…Although ADT has relevant impact on clinical practice, there is no consensus between imaging experts. We conducted a literature search on PubMed® and Google Scholar® in April 2019 and selected 19 papers (Table 1): 7 in vitro studies [3,4,[16][17][18][19][20], 2 in vivo studies [5,21], 4 prospective clinical studies [8][9][10][11], 2 reviews (clinical [6] and preclinical [7]), 2 retrospective clinical studies [12,13], 1 pilot clinical study [14] and 1 clinical case [15]. Additionally, we found 5 registered clinical trials (NCT03313726 [22], NCT03876912, NCT03860987, EudraCT 2018-004853-26 and EudraCT 2017-002345-29).…”

“…ADT led to different levels of increased PSMA uptake on PET, ranging from faint (17% [8]) to high increases (7-fold [11]) compared with baseline. Many papers stated that PSMA uptake was dependent on patients' castration status, but no consensus was established.…”

The Future of PSMA-Targeted Radionuclide Therapy: An Overview of Recent Preclinical Research

“…PSMA expression is thought to be regulated by androgens although reports showed conflicting results. While several studies have reported an increase in the level of PSMA expression in PCa cell-lines and in tumor tissue of patients after ADT [101,102,103], others describe a downregulation of PSMA expression caused by ADT [104,105]. Preclinical in vivo studies have so far been unsuccessful in showing an additive therapeutic effect on the tumor growth of this combination therapy [106].…”

Diagnostic Performance of [18F]Fluorocholine and [68Ga]Ga-PSMA PET/CT in Prostate Cancer: A Comparative Study

“…This may be the reason why the DR of [ 18 F]Fluorocholine PET/CT was more than [ 68 Ga]Ga-PSMA PET/CT in these two patients. Other possible explanations for the higher detection rate of [ 18 F]Fluorocholine PET/CT compared to [ 68 Ga]Ga-PSMA PET/CT include the superiority of [ 18 F]Fluorocholine PET/CT in the detection of bone metastases in poorly differentiated prostate cancers, and its ability to detect extra nodes that have begun the process of dedifferentiation [ 30 , 31 , 32 ]. However, a clear conclusion cannot be drawn due to the limited number of patients and lack of histopathological examination of the metastases.…”