A targeted low molecular weight near-infrared fluorescent probe for prostate cancer.

Prostate-specific membrane antigen (PSMA) remains an active target for imaging and therapeutic applications for prostate cancer. Although radionuclide-based imaging is generally more sensitive and also has been deeply explored, near-infrared fluorescence imaging agents are simple to prepare and compatible with long-term storage conditions. In the present study, a near-infrared fluorescent imaging probe (Cy5.5-CTT-54.2) has been developed by chemical conjugation of Cy5.5N-hydroxysuccinimide ester (Cy5.5-NHS) with a potent PSMA inhibitor CTT-54.2 (IC(50)=144 nM). The probe displays a highly potency (IC(50)=0.55 nM) against PSMA and has demonstrated successful application for specifically labeling PSMA-positive prostate cancer cells in both two and three-dimensional cell culture conditions. These results suggest that the potent, near-infrared Cy5.5-PSMA inhibitor conjugate may be useful for the detection of prostate tumor cells by optical in vivo imaging.

[1]  N. Bander,et al.  Constitutive and antibody-induced internalization of prostate-specific membrane antigen. , 1998, Cancer research.

[2]  Tiancheng Liu,et al.  Targeted photodynamic therapy for prostate cancer: inducing apoptosis via activation of the caspase-8/-3 cascade pathway. , 2010, International journal of oncology.

[3]  Philip S Low,et al.  Design, synthesis, and preclinical evaluation of prostate-specific membrane antigen targeted (99m)Tc-radioimaging agents. , 2009, Molecular pharmaceutics.

[4]  Hisataka Kobayashi,et al.  Clinical implications of near-infrared fluorescence imaging in cancer. , 2009, Future oncology.

[5]  G. Murphy,et al.  Isolation and characterization of monoclonal antibodies specific for the extracellular domain of prostate specific membrane antigen. , 1998, The Journal of urology.

[6]  Tiancheng Liu,et al.  Cell‐Surface labeling and internalization by a fluorescent inhibitor of prostate‐specific membrane antigen , 2008, The Prostate.

[7]  J. Frangioni,et al.  Multivalent scaffolds for affinity maturation of small molecule cell surface binders and their application to prostate tumor targeting. , 2009, Journal of medicinal chemistry.

[8]  C. Berkman,et al.  Probing for a hydrophobic a binding register in prostate-specific membrane antigen with phenylalkylphosphonamidates. , 2004, Bioorganic & medicinal chemistry.

[9]  J. Coyle,et al.  Prostate-specific membrane antigen is a hydrolase with substrate and pharmacologic characteristics of a neuropeptidase. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[10]  S. Vallabhajosula,et al.  Vascular targeted therapy with anti-prostate-specific membrane antigen monoclonal antibody J591 in advanced solid tumors. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  H. Beltran,et al.  Anti–prostate‐Specific membrane antigen‐based radioimmunotherapy for prostate cancer , 2010, Cancer.

[12]  W. Fair,et al.  Expression of the prostate-specific membrane antigen. , 1994, Cancer research.

[13]  H. VanBrocklin,et al.  Assessment of an 18F-Labeled Phosphoramidate Peptidomimetic as a New Prostate-Specific Membrane Antigen–Targeted Imaging Agent for Prostate Cancer , 2009, Journal of Nuclear Medicine.

[14]  Rolf Hilgenfeld,et al.  Human glutamate carboxypeptidase II inhibition: structures of GCPII in complex with two potent inhibitors, quisqualate and 2-PMPA. , 2007, Acta crystallographica. Section D, Biological crystallography.

[15]  Tiancheng Liu,et al.  Purification of prostate-specific membrane antigen using conformational epitope-specific antibody-affinity chromatography. , 2006, Protein expression and purification.

[16]  J. Konvalinka,et al.  Structural basis of interactions between human glutamate carboxypeptidase II and its substrate analogs. , 2008, Journal of molecular biology.

[17]  Zhen Cheng,et al.  Near-infrared fluorescent deoxyglucose analogue for tumor optical imaging in cell culture and living mice. , 2006, Bioconjugate chemistry.

[18]  V. Reuter,et al.  Prostate-specific membrane antigen is produced in tumor-associated neovasculature. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[19]  Martin G Pomper,et al.  Preclinical evaluation of novel glutamate-urea-lysine analogues that target prostate-specific membrane antigen as molecular imaging pharmaceuticals for prostate cancer. , 2009, Cancer research.

[20]  V. Reuter,et al.  Comparison of anti-prostate-specific membrane antigen antibodies and other immunomarkers in metastatic prostate carcinoma. , 2001, Urology.

[21]  Wei Chen,et al.  Effects of potential calcium sensing receptor inducers on promoting chemosensitivity of human colon carcinoma cells. , 2010, International journal of oncology.

[22]  W. Tong,et al.  Cloning, expression, genomic localization, and enzymatic activities of the mouse homolog of prostate-specific membrane antigen/NAALADase/folate hydrolase , 2001, Mammalian Genome.

[23]  Martin G Pomper,et al.  A low molecular weight PSMA-based fluorescent imaging agent for cancer. , 2009, Biochemical and biophysical research communications.

[24]  J. Neale,et al.  NAAG peptidase inhibitors and their potential for diagnosis and therapy , 2005, Nature Reviews Drug Discovery.

[25]  Tiancheng Liu,et al.  In vitro targeted photodynamic therapy with a pyropheophorbide‐a conjugated inhibitor of prostate‐specific membrane antigen , 2009, The Prostate.

[26]  Mindy I. Davis,et al.  Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[27]  S. Larson,et al.  Phase I Evaluation of J591 as a Vascular Targeting Agent in Progressive Solid Tumors , 2007, Clinical Cancer Research.

[28]  Shankar Vallabhajosula,et al.  Phase I trial of 177lutetium-labeled J591, a monoclonal antibody to prostate-specific membrane antigen, in patients with androgen-independent prostate cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  T. Tsukamoto,et al.  Progress in the discovery and development of glutamate carboxypeptidase II inhibitors. , 2007, Drug discovery today.

[30]  W. Schultze‐Seemann,et al.  Three conformational antibodies specific for different PSMA epitopes are promising diagnostic and therapeutic tools for prostate cancer , 2009, The Prostate.

[31]  A. Waggoner,et al.  Cyanine-labeling reagents: sulfobenzindocyanine succinimidyl esters. , 1996, Bioconjugate chemistry.

[32]  Takashi Tsukamoto,et al.  High-affinity Near-infrared Fluorescent Small-molecule Contrast Agents for In Vivo Imaging of Prostate-specific Membrane Antigen , 2005, Molecular imaging.

[33]  Tiancheng Liu,et al.  Pseudoirreversible inhibition of prostate-specific membrane antigen by phosphoramidate peptidomimetics. , 2008, Biochemistry.

[34]  J. Konvalinka,et al.  Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer , 2006, The EMBO journal.