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89Zr-Desferrioxamine B-7E11 anti-prostate-specific membrane antigen monoclonal antibody

, PhD
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD
Corresponding author.

Created: ; Last Update: February 23, 2012.

Chemical name:89Zr-Desferrioxamine B-7E11 anti-prostate-specific membrane antigen monoclonal antibody
Abbreviated name:89Zr-DFO-7E11
Agent category:Antibody
Target:Prostate-specific membrane antigen (PSMA), or N-acetyl α-linked acidic dipeptidase (NAALADase)
Target category:Antigen
Method of detection:Positron emission tomography (PET)
Source of signal:89Zr
  • Checkbox In vitro
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Click on protein, nucleotide (RefSeq), and gene for more information about PSMA.



Prostate-specific membrane antigen (PSMA) is a cell-surface glycoprotein with a molecular weight of ~100 kDa. It is a unique, type II, transmembrane-bound glycoprotein that is overexpressed on prostate tumor cells and in the neovasculature of most solid prostate tumors, but not in the vasculature of normal tissues (1, 2). PSMA has also been detected in other tissues such as the kidneys, the proximal small intestine, and the salivary glands (2). PSMA has been found to have N-acetyl α-linked acidic dipeptidase (NAALADase) or glutamate carboxypeptidase II activity (3). PSMA may play an important role in the progression of prostate cancer and glutamatergic neurotransmission, as well as in the absorption of folate (4). In the central nervous system, PSMA metabolizes N-acetyl-aspartyl-glutamate, and in the proximal small intestine it removes γ-linked glutamates from poly-γ-glutamate folate and folate hydrolase (2). This unique expression of PSMA makes it an important biomarker as well as a large extracellular target of imaging agents (5, 6). PSMA can be used as a biomarker for the detection of prostate cancer with imaging agents.

7E11, a monoclonal antibody against the cytoplasmic domain of PSMA, has been found to be specific to prostate tumor tissues in humans (7). Tumors often contain dying or necrotic cells with permeable membranes, allowing the binding of antibodies to the intracellular epitope of PSMA. The antibody conjugate (capromab pendetide or CYT-365) was radiolabeled with 111In. 111In-Capromomab pendetide was approved by the United States Food and Drug Administration in 1996 for the detection of prostate carcinoma and soft tissue metastases in prostate cancer patients (8). However, the results obtained with this antibody are not entirely reliable (9). In addition, this antibody has limited access to tumors and may produce low signal/noise ratios because the target is the intracellular domain of PSMA (10). Newer monoclonal antibodies (e.g., J591) against the extracellular domain of PSMA are being developed for imaging and immunotherapy of prostate cancer (11, 12). Ruggiero et al. (13) conjugated 7E11 with desferrioxamine B (DFO) and radiolabeled the product with 89Zr to form 89Zr-DFO-7E11 for positron emission tomography (PET) imaging of PSMA expression as a marker for dead or dying prostate tumor cells.



7E11-C5 was coupled with N-SucDf via an amide linkage (13). DFO-7E11 was purified with column chromatography. DFO-7E11 (4.9 nmol) was labeled with 138.8 MBq (3.75 mCi) 89Zr-oxalate for ~60 min at room temperature with a high yield of 89% (n = 4). 89Zr-DFO-7E11 was purified with spin-column centrifugation and retained 89% immunoreactivity. The radiochemical purity was >95% with a specific activity was ~25 MBq/nmol (0.68 mCi/nmol). The number of DFO moieties per antibody was 2.6 ± 0.5. 89Zr-DFO-7E11 showed <2% loss of 89Zr and no loss of immunoreactivity in saline at 37°C for 7 d.

In Vitro Studies: Testing in Cells and Tissues


LNCaP human prostate cancer cells were reported to have a Kd value of 6.69 nm with [131I]7E11-C5 and a Bmax value of 95,000 sites/cell in saturation binding studies (14) using intact cells. The binding was accounted for by a subpopulation of permeated cells produced when the cells were trypsinized and washed. Little internalization of the tracer was found over a period of 48 h at 37°C. When permeated cells were used, the number of binding sites/cell was similar to [131I]J591, an antibody against the extracellular domain of PSMA. Using nonpermeated cells, [131I]J591 has a Kd of 1.83 nm and a Bmax of 600,000–800,000 sites/cell.

Ruggiero et al. (13) performed flow cytometry and fluorescence microscopy analysis of PSMA-positive prostate cancer cells after treatments with etoposide (chemotherapy), flutamide (anti-androgen hormonal therapy), and irradiation radiotherapy. There was an increase in the percentage of cells stained with 7E11 and 7-amino-actinomycin-D (7-AAD for cell membrane permeabilization and viability assessment) with all treatments over time (24–120 h). There was a colocalization of 7E11 and caspase 3 staining in the cells at 96 h after treatments.

Animal Studies



Ruggiero et al. (13) performed ex vivo biodistribution studies with 0.55–0.74 MBq (0.015–0.02 mCi, 20–26 pmol) 89Zr-DFO-7E11 in nude mice (n = 5 per group) bearing LnCaP (PSMA-positive) bilateral tumors. One of the tumors in each mouse received radiotherapy (20 Gy). The accumulation in the untreated LnCaP tumors was 20.4 ± 7.5% injected dose per gram (ID/g), 22.8 ± 3.6% ID/g, 37.0 ± 6.3% ID/g, and 25.2 ± 4.8% ID/g at 24, 48, 96, and 120 h after injection, respectively. The accumulation in the treated LnCaP tumors was 24.7 ± 7.2% ID/g, 40.6 ± 7.5% ID/g, 51.8 ± 7.4% ID/g, and 52.7 ± 11.1% ID/g at 24, 48, 96, and 120 h after injection, respectively. The higher accumulation values in the treated tumors than in the untreated tumors were statistically significant (P < 0.05) with the exception of the 24-h time point. The tissue with the highest accumulation at 48 h after injection was the liver (42.7% ID/g), followed by the spleen (29.9% ID/g), kidney (21.6% ID/g), lung (7.6% ID/g), bone (6.3% ID/g), intestine (4.9% ID/g), heart (4.7% ID/g), and muscle (1.0% ID/g). The radioactivity level in the blood was 32.6% ID/g at 24 h and declined to 6.6% ID/g at 120 h. The tumor/blood ratios were 1.8 and 1.0 at 48 h for the treated and untreated tumors, respectively. Coinjection with excess 7E11 (2.0 nmol) reduced the tumor/blood ratios by ~60% to 0.5 and 0.4 at 48 h for the treated and untreated tumors. Autoradiography studies of the tumor sections showed higher accumulation of 89Zr-DFO-7E11 in the treated tumors than in the untreated tumors. Immunochemical staining showed colocalization of 7E11 with apoptotic (caspase 3) and necrotic areas (hematoxylin and eosin) in the treated tumor sections.

PET imaging in nude mice (n = 5) with ~11 MBq (0.3 mCi) 89Zr-DFO-7E11 (0.44 nmol per mouse) visualized both the untreated and treated LnCaP tumors as early as 24 h after injection with a maximum contrast at 72 h (13). The accumulation in the untreated LnCaP tumors was 14.7 ± 5.7% ID/g, 14.7 ± 6.3% ID/g, 19.1 ± 7.3% ID/g, 15.6 ± 7.9% ID/g, and 14.8 ± 8.1% ID/g at 24, 48, 72, 96, and 120 h after injection, respectively. The accumulation in the treated LnCaP tumors was 21.6 ± 2.5% ID/g, 29.9 ± 2.3% ID/g, 31.8 ± 3.8% ID/g, 30.7 ± 5.0% ID/g, and 31.4 ± 5.3% ID/g at 24, 48, 72, 96, and 120 h after injection, respectively. The accumulation values in the treated tumors were significantly higher (P < 0.05) than in the untreated tumors at all the time points studied.

Other Non-Primate Mammals


No publication is currently available.

Non-Human Primates


No publication is currently available.

Human Studies


No publication is currently available.

NIH Support

U24 CA83084, P30 CA008748-44S5, P30 CA08748, R25T CA096945


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