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Technology Insight: monoclonal antibody imaging of prostate cancer

Abstract

Imaging is a critical component of diagnosis, staging and monitoring, all of which factor heavily in treatment decision-making for cancer patients. Agents, such as antibodies, can target molecules that are relatively unique to cancer cells. Prostate-specific membrane antigen (PSMA) is the most well-established, highly restricted prostate-cancer-related cell membrane antigen known. Ten years ago, the FDA approved 111In-capromab pendetide for use in imaging soft-tissue, but not bone, sites of metastatic prostate cancer for presurgical staging or the evaluation of PSA relapse after local therapy. For presurgical patients with high-risk disease but negative bone, CT and MRI scans, capromab demonstrated the ability to identify some patients with positive nodes, thereby sparing them an unnecessary surgical procedure. But there have been no follow-up studies to indicate that high-risk patients with a negative capromab scan have a lower failure rate after surgery. In the setting of PSA relapse, capromab is compromised by its inability to sensitively image bone metastases; bone is the first site of metastatic prostate cancer in 72% of patients. The problem with imaging bone metastases is that capromab detects an antigenic site on the intracellular portion of PSMA—a site not accessible to circulating antibodies. Early results indicate that second-generation antibodies that target the extracellular domain of PSMA might provide significant benefits in the imaging of prostate cancer.

Key Points

  • Prostate-specific membrane antigen (PSMA) is the most well-established, highly restricted prostate cancer-related cell membrane antigen known

  • In 1996, the FDA approved 111In-capromab pendetide (capromab) for imaging soft-tissue, but not bone, sites of metastatic prostate cancer

  • Capromab detects an antigenic site on the intracellular portion of PSMA, a site not accessible to circulating antibody, which thus explains its inability to bind to well-vascularized metastases in the bone marrow

  • The utility of capromab is compromised by its inability to sensitively image bone metastases, as bone is the first site of metastatic prostate cancer spread in approximately 75% of patients

  • The inability to image bone metastases probably explains the inconsistent results reported on the use of capromab for staging patients with PSA relapse

  • Early results indicate that second-generation antibodies that target the extracellular domain of PSMA are able to target and image bone metastases, and, therefore, might provide significant benefits when imaging prostate cancer

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Figure 1: Schematic representation of prostate-specific membrane antigen and epitopes of capromab and J591.
Figure 2: Scans of two patients with metastatic prostate cancer.
Figure 3: Bone and 177Lutetium-J591 scans, performed 10 days apart.
Figure 4: Bone, 177Lutetium-J591 and MRI scans.
Figure 5: Antibody scans of two patients who each received two doses of 177Lutetium-J591.

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Correspondence to Neil H Bander.

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Competing interests

Neil H Bander developed monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen and assigned patent rights to Cornell Research Foundation. These patents were licensed to BZL Biologics Inc. Neil H Bander is a paid consultant to BZL Biologics Inc.

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Bander, N. Technology Insight: monoclonal antibody imaging of prostate cancer. Nat Rev Urol 3, 216–225 (2006). https://doi.org/10.1038/ncpuro0452

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