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EJNMMI Research
Published in: EJNMMI Research 1/2015

Open Access 01-12-2015 | Original research

Indium 111-labeled J591 anti-PSMA antibody for vascular targeted imaging in progressive solid tumors

Authors: Neeta Pandit-Taskar, Joseph A O’Donoghue, Chaitanya R Divgi, Eze A Wills, Lawrence Schwartz, Mithat Gönen, Peter Smith-Jones, Neil H Bander, Howard I Scher, Steven M Larson, Michael J Morris

Published in: EJNMMI Research | Issue 1/2015

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Abstract

Background

J591 is a monoclonal antibody that targets the external domain of the prostate-specific membrane antigen (PSMA). Besides prostate cancer cells, it also targets the neovasculature of non-prostate solid tumors. We provide an analysis of the antibody mass-dose dependency of lesion uptake and normal tissue retention, together with an assessment of lesion detectability using 111In-J591 imaging, compared with conventional imaging in patients with a variety of solid tumors.

Methods

Twenty patients in six cohorts received fixed amounts (5, 10, 20, 40, 60, and 100 mg) of J591 in a phase I trial. A maximum of four administrations per patient was given, with each administration separated by 3 weeks. All antibody administrations included 370 MBq (10 mCi) of 111In labeled to 2 mg of J591 via the chelating agent DOTA. Three whole body (WB) gamma camera scans with at least one SPECT scan, along with multiple WB count-rate measurements and blood samples, were obtained for all patients. The effect of escalating antibody mass on lesion uptake and normal tissue retention was evaluated using lesion, liver, serum, and WB residence times and ratios thereof for each treatment cycle. Lesion detectability using 111In-J591 imaging was compared to the standard imaging on a lesion-by-lesion basis.

Results

A total of 170 lesions in 20 patients were detected by standard or 111In-J591 imaging. 111In-J591 targeted both skeletal and soft tissue diseases in all tumor types. 111In-J591 imaging identified 74% (20/27) of skeletal lesions, 53% (18/34) of nodes, and 64% (70/109) of other soft tissue/organ lesions. There was increasing 111In-J591 uptake in lesions with increasing antibody mass-dose, coupled with decreasing retention in the liver for increments up to 20 mg, and no significant change at higher antibody mass.

Conclusions

Radiolabeled J591 antibody has potential as a targeting agent for solid tumor vasculature and lesion detection. Bone and soft tissue lesions arising from tumors of diverse origin were targeted by the anti-PSMA antibody J591. For the detection of lesions in these tumors by J591 antibody scans, an antibody mass of 20 mg is adequate. The optimal time of imaging is 5 to 7 days post-injection.
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Metadata
Title
Indium 111-labeled J591 anti-PSMA antibody for vascular targeted imaging in progressive solid tumors
Authors
Neeta Pandit-Taskar
Joseph A O’Donoghue
Chaitanya R Divgi
Eze A Wills
Lawrence Schwartz
Mithat Gönen
Peter Smith-Jones
Neil H Bander
Howard I Scher
Steven M Larson
Michael J Morris
Publication date
01-12-2015
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2015
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-015-0104-4

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