A series of halogenated heterodimeric inhibitors of prostate specific membrane antigen (PSMA) as radiolabeled probes for targeting prostate cancer

K. P. Maresca, S. M. Hillier, F. J. Femia, D. Keith, C. Barone, J. L. Joyal, C. N. Zimmerman, A. P. Kozikowski, J. A. Barrett, W. C. Eckelman, J. W. Babich

Research output: Contribution to journalArticle

Abstract

Prostate specific membrane antigen (PSMA) is a validated molecular marker for prostate cancer. A series of glutamate-urea (Glu-urea-X) heterodimeric inhibitors of PSMA were designed and synthesized where X = ε-N-(o-I, m-I, p-I, p-Br, o-Cl, m-Cl, p-Cl, p-F, H)-benzyl-Lys and ε-(p-I, p-Br, p-Cl, p-F, H)-phenylureido- Lys. The affinities for PSMA were determined by screening in a competitive binding assay. PSMA binding of the benzyllysine series was significantly affected by the nature of the halogen substituent (IC 50 values, Cl <I = Br « F = H) and the ring position of the halogen atom (IC 50 values, p-I <o-I « m-I). The halogen atom had little affect on the binding affinity in the para substituted phenylureido-Lys series. Two lead iodine compounds were radiolabeled with 123I and 131I and demonstrated specific PSMA binding on human prostate cancer cells, warranting evaluation as radioligands for the detection, staging, and monitoring of prostate cancer.

Original languageEnglish (US)
Pages (from-to)347-357
Number of pages11
JournalJournal of Medicinal Chemistry
Volume52
Issue number2
DOIs
StatePublished - Jan 22 2009
Externally publishedYes

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Prostatic Neoplasms
Halogens
Urea
Iodine Compounds
Competitive Binding
Glutamic Acid
human glutamate carboxypeptidase II

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

A series of halogenated heterodimeric inhibitors of prostate specific membrane antigen (PSMA) as radiolabeled probes for targeting prostate cancer. / Maresca, K. P.; Hillier, S. M.; Femia, F. J.; Keith, D.; Barone, C.; Joyal, J. L.; Zimmerman, C. N.; Kozikowski, A. P.; Barrett, J. A.; Eckelman, W. C.; Babich, J. W.

In: Journal of Medicinal Chemistry, Vol. 52, No. 2, 22.01.2009, p. 347-357.

Research output: Contribution to journalArticle

Maresca, KP, Hillier, SM, Femia, FJ, Keith, D, Barone, C, Joyal, JL, Zimmerman, CN, Kozikowski, AP, Barrett, JA, Eckelman, WC & Babich, JW 2009, 'A series of halogenated heterodimeric inhibitors of prostate specific membrane antigen (PSMA) as radiolabeled probes for targeting prostate cancer', Journal of Medicinal Chemistry, vol. 52, no. 2, pp. 347-357. https://doi.org/10.1021/jm800994j
Maresca, K. P. ; Hillier, S. M. ; Femia, F. J. ; Keith, D. ; Barone, C. ; Joyal, J. L. ; Zimmerman, C. N. ; Kozikowski, A. P. ; Barrett, J. A. ; Eckelman, W. C. ; Babich, J. W. / A series of halogenated heterodimeric inhibitors of prostate specific membrane antigen (PSMA) as radiolabeled probes for targeting prostate cancer. In: Journal of Medicinal Chemistry. 2009 ; Vol. 52, No. 2. pp. 347-357.
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