Abstract CT413: Lutetium-177-labeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (177Lu-J591) for metastatic non-prostate solid tumors
Authors: Pail Orrin , Kaur Gurveen , Dyke Jonathan , Jhanwar Yuliya , Christos Paul , Ocean Allyson , Shah Manish , Shore Tsiporah , Schneider Bryan , Scheff Ronald , Beltran Himisha , Ballon Douglas , Robinson Brian , Nanus David M. , Bander Neil H. , Tagawa Scott T. 
Published: May 2015

Abstract
Introduction: PSMA is a non-secreted cell-surface protein that is expressed by the neovascular endothelium of most solid tumors (but not by vascular endothelium of normal tissue), making it a candidate for vascular-targeted therapy. The purpose of this study was to define the change in tumor perfusion and cellularity after 177Lu-J591 therapy in patients (pts) with advanced non-prostate solid tumors and PSMA expression as determined by radionuclide imaging (with 111In-J591) and/or by immunohistochemistry (IHC). Of note, radiolabeled J591 is hepatically cleared (negating accurate assessment of liver metastases by J591 imaging).
Methods: In this pilot study, following confirmation of PSMA expression by 111In-J591 imaging and/or IHC of tumor neovasculature), 14 pts in 2 cohorts received 177Lu-J591 therapy (7 received a single dose at 70 mCi/m2; 7 received 2 fractionated doses at 35 mCi/m2 each). Pts underwent dynamic contrast enhanced (DCE)-MRI and diffusion weighted imaging (DWI) at baseline, then repeated at 1, 4, 8, and 12 wks post treatment to evaluate tumor perfusion (DCE-MRI) and cellularity (Apparent Diffusion Coefficient (ADC) values from DWI). Values were compared with paired t-testing using Wilcoxon signed-rank test for significance.
Results: Among the 14 treated pts, tumor types included: lung (5), bladder (2), pancreas (2), colon, GE junction, renal, ovarian carcinomas and melanoma (1 each). Median age was 61.5 with a median of 3 prior therapies including 5 with prior anti-angiogenic agents; 8 pts received prior radiation. Metastatic sites included: bone, lymph nodes, liver, lung, brain, other. 11 of 14 pts had PSMA expression confirmed by imaging, 3 additional by IHC of archival tumor tissue (with liver metastases).
DCE-MRI demonstrated that treatment significantly affected tumor perfusion, with decreased perfusion at the 1-wk (n=11, p=0.03) and 4-wk (n=6, p=0.01) post 177Lu-J591 time points. Compared to baseline, DCE slope was lower than baseline at 1 wk (p=0.045) and 4-wk (p=0.02). Week 8 (n=4) was non-significant for both % change and DCE slope and only 2 pts completed the wk 12 time point.
In evaluation of cellularity, 5 of 9 pts had an increase in ADC at either the 1- or 4-wk time point (1 stable, 3 decreased). However, paired comparisons at individual time points were non-significant.
Conclusion: Anti-PSMA radioimmunotherapy targeting tumor neovasculature is feasible using 177Lu-J591 and can alter tumor perfusion and cellularity, including in those with prior exposure to anti-angiogenic therapy and/or radiation. Refinement in patient selection with improved imaging (anti-PSMA immuno-PET) is ongoing.
Citation Format: Orrin Pail, Gurveen Kaur, Jonathan Dyke, Yuliya Jhanwar, Paul Christos, Allyson Ocean, Manish Shah, Tsiporah Shore, Bryan Schneider, Ronald Scheff, Himisha Beltran, Douglas Ballon, Brian Robinson, David M. Nanus, Neil H. Bander, Scott T. Tagawa. Lutetium-177-labeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (177Lu-J591) for metastatic non-prostate solid tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT413. doi:10.1158/1538-7445.AM2014-CT413