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 (111)In-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.

N-[N-[(S)-1,3-Dicarboxypropyl]Carbamoyl]-4-[18F]Fluorobenzyl-l-Cysteine, [18F]DCFBC: A New Imaging Probe for Prostate Cancer

“…Like ProstaScint, [ 18 F]DCFBC binds to PSMA, the most wellestablished and highly restricted prostate cancer -related membrane antigen (26). PSMA is up-regulated in prostate cancer, particularly in advanced, hormone-independent, and metastatic disease (27,28).…”

Evaluation of Hybrid 68Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy

“…The localization of the catalytic site of PSMA in the extracellular domain allows the development of small specific inhibitors that are internalized after ligand binding (14). Older agents targeting the intracellular domain of PSMA showed disappointing results due to low image contrast, low sensitivity, or high background signal (15). The recent development of 68 Ga-PSMA (Glu-NH-CO-NH-Lys-(Ahx)-[ 68 Ga(HBED-CC)]) as an extracellular PSMA inhibitor for PET imaging demonstrated a high specificity for PSMA tumor-expressing cells as well a high and specific uptake in a mouse model (16).…”

PSMA Ligands for PET Imaging of Prostate Cancer

“…PSMA expression levels increase with higher tumor stage and grade (16,18,22). Presently, the only Food and Drug Administration-approved PSMA agent is a radiolabeled anti-PSMA antibody (ProstaScint, capromab pendetide; EUSA Pharma); however, this targets an intracellular epitope of PSMA (7E11) (19) that cannot be accessed in viable tumor cells, limiting diagnostic performance (23).…”