Prostate-specific membrane antigen-based imaging.
Prostate cancer (CaP) is the most common noncutaneous malignancy affecting men in North America. Despite significant efforts, conventional imaging of CaP does not contribute to patient management as much as imaging performed for other common cancers. Given the lack of specificity in conventional imaging techniques, one possible solution is to screen for CaP-specific antigenic targets and generate agents able to specifically bind. Prostate-specific membrane antigen (PSMA) is overexpressed in CaP tissue, with low levels of expression in the small intestine, renal tubular cells, and salivary gland. The first clinical agent for targeting PSMA was (111)In-capromab, involving an antibody recognizing the internal domain of PSMA. The second- and third-generation humanized PSMA binding antibodies have the potential to overcome some of the limitations inherent to capromab penditide (i.e., inability to bind to live CaP cells). One example is the humanized monoclonal antibody J591 (Hu mAb J591) that was developed primarily for therapeutic purposes but also has interesting imaging characteristics, including the identification of bone metastases in CaP. The major disadvantage of use of mAb for imaging is slow target recognition and background clearance in an appropriate time frame for diagnostic imaging. Urea-based compounds, such as small molecule inhibitors may also present promising agents for CaP imaging with single-photon emission computed tomography (SPECT) and positron emission tomography (PET). Two such small-molecule inhibitors targeting PSMA, MIP-1072, and MIP-1095 have exhibited high affinity for PSMA. The uptake of (123)I-MIP-1072 and (123)I-MIP-1095 in CaP xenografts have imaged successfully with favorable properties amenable to human trials. While advances in conventional imaging will continue, Ab and small molecule imaging exemplified by PSMA targeting have the greatest potential to improve diagnostic sensitivity and specificity.
Department of Radiology, Weill Cornell Medical College, New York, NY 10065, USA.
Joseph R
JR
Osborne
Naveed H
NH
Akhtar
Shankar
S
Vallabhajosula
Alok
A
Anand
Kofi
K
Deh
Scott T
ST
Tagawa
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D043425:Glutamate Carboxypeptidase II / Q000032:analysis*; D006801:Humans; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging*; D019275:Radiopharmaceuticals; D015899:Tomography, Emission-Computed, Single-Photon
D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D019275:Radiopharmaceuticals; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II