A Series of Halogenated Heterodimeric Inhibitors of Prostate Specific Membrane Antigen (PSMA) as Radiolabeled Probes for Targeting Prostate Cancer

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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 (IC₅₀ values, Cl < I = Br F = H) and the ring position of the halogen atom (IC₅₀ 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.

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This article has been cited by 4 ACS Journal articles (4 most recent appear below).

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    Abstract | Full Text HTML | Hi-Res PDF | PDF w/ Links
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  Fluorous Isocyanates: Convenient Synthons for the Preparation of Radioiodinated Compounds in High Effective Specific Activity

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  • Fluorous Isocyanates: Convenient Synthons for the Preparation of Radioiodinated Compounds in High Effective Specific Activity

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    Abstract | Full Text HTML | Hi-Res PDF | PDF w/ Links
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  Comprehensive Radiolabeling, Stability, and Tissue Distribution Studies of Technetium-99m Single Amino Acid Chelates (SAAC)

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    Abstract | Full Text HTML | Hi-Res PDF | PDF w/ Links

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