Abstract 4696: Non-invasive measurement of prostate-specific membrane antigen (PSMA) expression with radiolabeled J591 imaging: a promising biomarker for PSMA-based radioimmunotherapy.
Authors: Akhtar Naveed H. , Osborne Joseph , Nanus David M. , Vallabhajosula Shankar , Goldsmith Stanley J. , Bander Neil H. , Tagawa Scott T. 
Published: August 2014

Background:

PSMA is nearly universally expressed by prostate cancer and is upregulated with castration-resistance. Recently, non-invasive measurement of PSMA expression has been demonstrated to be a novel biomarker of androgen receptor activity in animal models. J591 is a monoclonal antibody which selectively and efficiently binds the external domain of PSMA with no direct effect on PSA expression or secretion. Four therapeutic phase I and II trials of radiolabeled (RL)-J591 using (177Lu-J591 and 90Y-J591) have been performed in men with metastatic castration-resistant prostate cancer (CRPC). In addition to therapeutic infusion with RL-J591, planar gamma camera imaging was performed.

Methods:

Following IRB approval, a combined analysis of 4 prospective studies of RL-J591 for metastatic CRPC was performed. RL-J591 images 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. In addition, a semi-quantitative Tissue Targeting Index (TTI) was calculated for the most prominent lesions in each subject using the ratio of lesion count density (corrected for background) to whole body count density, with maximum and mean scores recorded. PSMA expression as measured by imaging was correlated with efficacy measures in long-term follow up of all studies.

Results:

130 patients (pts) with metastatic CRPC received RL- J591 with semi-quantitative 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. Only 8.0% of pts with no evidence of PSMA expression via J591 imaging (VS=0) experienced treatment response versus 40.6% of those with the highest strongest expression as measured by VS (p=0.01). In addition to PSA declines, for the subset of 17 pts with baseline and follow up circulating tumor cell (CTC) counts, those with higher VS tended to have more CTC decreases (p=0.12). Those with the lowest level of PSMA expression as measured by TTI tended to have fewer PSA declines (p=0.12). PSA response was associated with superior overall survival compared to those without &gt;30% PSA decline (p=0.02).

Conclusions:

Non-invasive measurement of PSMA expression may be semi-quantitatively measured with planar gamma-camera imaging following infusion with RL-J591. Level of PSMA expression is associated with response to radiolabeled anti-PSMA radioimmunotherapy. Improvements in quantitative molecular imaging techniques such as PSMA PET/CT with 89Zr-J591 may prove to be a valuable predictive biomarker for PSMA-based therapeutics.

Citation Format: Naveed H. Akhtar, Joseph Osborne, David M. Nanus, Shankar Vallabhajosula, Stanley J. Goldsmith, Neil H. Bander, Scott T. Tagawa. Non-invasive measurement of prostate-specific membrane antigen (PSMA) expression with radiolabeled J591 imaging: a promising biomarker for PSMA-based radioimmunotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4696. doi:10.1158/1538-7445.AM2013-4696