Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012;19(9):1346-59.
doi: 10.2174/092986712799462612.

GCPII imaging and cancer

C A Foss  1 , R C Mease, S Y Cho, H J Kim, M G Pomper
Affiliations
Review

GCPII imaging and cancer

C A Foss et al. Curr Med Chem. 2012.

Abstract

Glutamate carboxypeptidase II (GCPII) in the central nervous system is referred to as the prostate-specific membrane antigen (PSMA) in the periphery. PSMA serves as a target for imaging and treatment of prostate cancer and because of its expression in solid tumor neovasculature has the potential to be used in this regard for other malignancies as well. An overview of GCPII/PSMA in cancer, as well as a discussion of imaging and therapy of prostate cancer using a wide variety of PSMA-targeting agents is provided.

PubMed Disclaimer

Figures

Fig. (1)
Fig. (1)
Diagram of PSMA-augmented generation of NO in nascent endothelial cells. PSMA folate hydrolase activity may boost NO production in two complementary ways including scavenging extra folate (orange circle) to increase BH4 eNOS cofactor turnover and generation of extra glutamate (stars), which raises intracellular calcium levels to increase expression of eNOS. NO is important for angiogenesis and expression of PSMA on neovasculature and may increase the efficiency of vessel formation.
Fig. (2)
Fig. (2)
Diagram of the possible consequences of PSMA folate hydrolase activity in prostate cancer cells. Scavenged poly-γ-glutamyl folate substrates could feed nearby or interacting mGluR1/5 or NMDARs with released glutamates, maintaining both the downstream activation of NF-γB and raising intracellular calcium levels indirectly through mGluR5 signaling or directly through NMDAR channel opening. Small amounts of glutamate might be beneficial while large amounts of glutamate could cause excitotoxicity.
Fig. (3)
Fig. (3)
FDG PET showing FDG uptake at sites of widely metastatic disease in a patient with advanced castrate-resistant prostate cancer. (A) liver metastases (white arrows); (B) lumbar and right pelvic bone metastases (white arrows). (Johns Hopkins PET center).
Fig. (4)
Fig. (4)
Phosphorus-containing GCPII imaging and therapeutic agents.
Fig. (5)
Fig. (5)
Urea-based GCPII imaging agents.
Fig. (6)
Fig. (6)
Optical and radiometallated GCPII imaging agents.
Fig. (7)
Fig. (7)
Additional urea-based imaging agents for GCPII.
See this image and copyright information in PMC

References

    1. Halsted CH. The intestinal absorption of folates. The American journal of clinical nutrition. 1979;32(4):846–55. - PubMed
    1. Sirotnak FM, Tolner B. Carrier-mediated membrane transport of folates in mammalian cells. Annual review of nutrition. 1999;19:91–122. - PubMed
    1. Fowler B. The folate cycle and disease in humans. Kidney International Supplement. 2001;78:S221–9. - PubMed
    1. Moran RG. Roles of folylpoly-gamma-glutamate synthetase in therapeutics with tetrahydrofolate antimetabolites: an overview. Seminars in Oncology. 1999;26(2 Suppl 6):24–32. - PubMed
    1. Ghosh A, Heston WD. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem. 2004;91(3):528–39. - PubMed

Publication types

MeSH terms