Noninvasive measurement of prostate-specific membrane antigen (PSMA) expression with radiolabeled J591 imaging: A prognostic tool for metastatic castration-resistant prostate cancer (CRPC).

Abstract

11081 Background: PSMA is nearly universally expressed by PC, upregulated with increased grade and castration-resistance. Evidence points towards PSMA expression as a downstream cellular biomarker of androgen receptor (AR) activity and non-invasive measurement of PSMA expression has recently been demonstrated to be a novel biomarker of AR activity. Methods: Planar gamma camera images following radiolabeled J591 (111In-J591 or 177Lu-J591) were semi-quantitatively scored using 2 methods by 2 independent radiologists blinded to outcome.A 5-point visual score (VS) of 0 - 4+ was assigned. Tissue Targeting Index (TTI), a novel metric designed to semi-quantitatively score images was calculated using the ratio of lesion count density (corrected for background) to whole body count density, with maximum (TTImax) and mean (TTIave) scores recorded. Follow up tabulating subsequent therapies and overall survival (OS) was recorded and imaging scores were associated with OS using Cox regression analysis. Results: 130 men with metastatic CRPC underwent radiolabeled J591 imaging. 86.2% had bone metastases, 51.5% lymph node, 16.9% lung, 9.2% liver. 87.7% had accurate targeting of known sites of disease by planar imaging. CALGB (Halabi) nomogram scores were prognostic for the population. As continuous variables, TTImax (p=0.013) and TTIave (p=0.002) were associated with worse survival. VS demonstrated a trend for worse survival (p=0.09). In multivariate analysis, TTI maintained independent prognostic value when controlling for Halabi score: TTImax HR 1.05 [95% CI 1.01, 1.10; p=0.02], TTIaveHR 1.09 [1.03, 1.16; p=0.004]. Conclusions: Level of PSMA expression measured by planar gamma-camera imaging following radiolabeled J591 is associated with OS in men with metastatic CRPC. High PSMA expression may indicate more aggressive tumor biology with increased AR pathway dysfunction. Improvements in quantitative molecular imaging techniques such as PSMA PET/CT with 89Zr-J591 may prove to be a valuable prognostic and predictive biomarker, particularly in the setting of AR- and PSMA-targeted therapy. Clinical trial information: NCT00195039, NCT00538668.