Nanobodies singledomain antibodies, v hh are the smallest antibodybased fragments possessing ideal molecular imaging properties, such as high target specificity and rapid background clearance. Prostatespecific membrane antigen radiology reference. Radiohalogenated prostate specific membrane antigen psmabased ureas as imaging agents for prostate cancer. Glutamate carboxypeptidase ii gcpii, also known as nacetyllaspartyllglutamate peptidase i naaladase i, naag peptidase, or prostatespecific membrane antigen psma is an enzyme that in humans is encoded by the folh1 folate hydrolase 1 gene. Prostatespecific membrane antigen psma is known to be highly overexpressed in prostate cancer cells, with high sensitivity for malignancy. Targeting of prostatespecific membrane antigen for radio. Pearls and pitfalls in clinical interpretation of prostate. Prostate specific membrane antigena target for imaging. Prostascint is an fda approved imaging agent for prostate cancer that has been in use since the late 1990s. Prostate cancer cells overexpress the prostatespecific membrane antigen psma receptors on the surface. Clinical research directorateclinical monitoring research program, leidos. Turkbey b1, mena e, lindenberg l, adler s, bednarova s, berman r, ton at, mckinney y, eclarinal p, hill c, afari g, bhattacharyya s, mease rc, merino mj, jacobs pm, wood bj, pinto pa.
Prostate specific membrane antigen psma targeted photoacoustic imaging of prostate cancer in vivo april 20, 2018 here we propose a molecular photoacoustic pa imaging approach by targeting the prostate specific membrane antigen psma, which is overexpressed in the vast majority of prostate cancers. Apr 28, 2015 second generation 18flabeled prostate specific membrane antigen psma targeted imaging agent found to be highly sensitive in detecting prostate cancer share article wmis to offer unlimited online access to article published in the journal of molecular imaging and biology. Psma has emerged as a useful target in pet imaging of prostate cancer, especially in the evaluation of small volume lymph node and bone metastases 2. Prostate specific membrane antigen psma also known as glutamate carboxypeptidase ii is a type ii transmembrane glycoprotein that has become an increasingly prominent imaging biomarker 1. Prostatespecific membrane antigen psma is a type ii cell surface glycoprotein that is upregulated in castrateresistant and metastatic prostate cancer. Imaging of prostatespecific membrane antigen with small.
Prostatespecific membrane antigen psma is overexpressed on the. The first clinical agent targeting psma in prostate cancer was prostascint capromab pendetide, eusa pharma elsasserbeile et al. Prostatespecific membrane antigen psma is overexpressed in prostate cancer pca and a promising target for molecular imaging and therapy. Prostatespecific membrane antigen ligands for imaging and therapy. Imaging car t cell therapy with psmatargeted positron. Radiochemistry and preclinical pet imaging of 68ga.
Synthesis and biological evaluation of low molecular weight fluorescent imaging agents for the prostatespecific membrane antigen. Several radioligands targeting prostatespecific membrane antigen psma have been clinically introduced as a new class of radiotheranostics for imaging and treating prostate cancer. Prostatespecific membrane antigen targeted therapy of prostate. As the first step in validating the applicability of prostatespecific membrane antigen psmatargeted imaging in highgrade gliomas, we evaluated the ability of the psmatargeted small molecule fdcfpyl 231carboxy56ffluoropyridine3carbonylaminopentylureidopentan edioic acid to image highgrade gliomas in a series of 3 prospectively recruited patients. Jun 11, 2018 apodox is both passively through enhanced permeability and retention effect and actively targeted to tumors through prostate specific membrane antigen psma via mouse antibodies conjugated to. Nearinfrared photoimmunotherapy nirpit is a highly selective tumor treatment that employs an antibodyphotoabsorber conjugate apc. Nov 08, 2018 prostate cancer radiotherapy more precisely targeted with nuclear medicine imaging. Prostate specific membrane antigen psma scanning is a sensitive method of prostate cancer detection.
Noninvasive, serial imaging of car t cell therapy using a reporter transgene can address those issues. Prostatespecific membrane antigen psma is a transmembrane protein commonly found on the surface of latestage and metastatic prostate cancer and a wellknown imaging biomarker for staging and monitoring therapy. New technique could optimize psmatargeted prostate cancer. Prostatespecific membrane antigen psma is typically highly expressed in prostate cancer, and the gluurealys gul structure has recently received considerable attention as a key unit of psmatargeting agents. The rapidly expanding clinical adaptation of prostate specific membrane antigen psma targeted pet imaging in the evaluation of patients with prostate cancer has placed an increasing onus on understanding both the potential pearls of interpretation as well as limitations of this new technique. Prostate specific membrane antigen psma is a wellcharacterized imaging biomarker of pca. We developed a prostatespecific membrane antigen psma targeted nearinfrared nir imaging agent otl78 that. Prostate specific membrane antigen psma is known to be highly overexpressed in prostate cancer cells, with high sensitivity for malignancy. Novel multifunctional 18flabelled pet tracer with prostate. Prostate cancer cells overexpress the prostate specific membrane antigen psma receptors on the surface. Prostate cancer is one of the most frequently found cancers in men worldwide. Prostatespecific membrane antigen psma is a transmembrane protein commonly. Prostate specific membrane antigen targeted 18fdcfpyl positron emission tomographycomputerized tomography for the preoperative staging of high risk prostate cancer.
Prostatespecific membrane antigen psma is an important target for nuclear medicine imaging of prostate cancer and subsequent psma targeted radionuclide therapy. Prostate specific membrane antigen psma is a cell surface enzyme that is highly expressed in prostate cancer pca and is currently being extensively explored as a promising target for molecular. A biodegradable probe made of dextran and a ureabased targeting ligand for prostatespecific membrane antigen enables targeted magnetic resonance imaging of tumours. Blue earth diagnostics announces dosing of first patient in. Pearls and pitfalls in clinical interpretation of prostatespecific membrane antigen psmatargeted pet imaging. Prostatespecific membrane antigen targeted polymersomes for. Here we present initial safety, biodistribution, and radiation dosimetry results with 18fdcfpyl, a secondgeneration fluorine18labeled smallmolecule psma inhibitor, in patients with prostate cancer. Imaging of prostate specific membrane antigen targeted radiotracers for. Targeted, activatable, in vivo fluorescence imaging of prostate specific membrane antigen psma positive tumors using the quenched humanized j591 antibodyindocyanine green icg conjugate. Given the number of studies that currently are underway. The prostatespecific membrane antigen psma is highly expressed on most prostate cancer pc cells. Psma is expressed on greater than 90% of all prostate cancers. Psma is a 68favorable target for imaging and radionuclide therapy of pca, because it is overexpressed in 90100% of local pca lesions, as well as in cancerous lymph node metastases and bone lesions. Biodistribution and radiation dosimetry for a probe targeting prostatespecific membrane antigen for imaging and therapy article pdf available in journal of nuclear medicine 566 april 2015.
Imaging of prostate specific membrane antigen targeted. Prostatespecific membrane antigen psmatargeted pet. Pdf prostatespecific membrane antigen expression in. Targeting the enzyme biomarker prostate specific membrane antigen psma on cancer is leading to exciting new imaging and therapeutic agents for prostate and other cancers. Prostatespecific membrane antigentargeted imaging with. Targeted, activatable, in vivo fluorescence imaging of prostatespecific membrane antigen psma positive tumors using the quenched humanized j591 antibodyindocyanine green icg conjugate. Radiotracers incorporating the ureabased glunhconhlys group have gained prominence due to their role in targeting prostatespecific membrane antigen psmaa clinical biomarker of prostate c. Background radiolabelled prostate specific membrane antigen psmabased petct or petmri is a wholebody imaging technique currently performed for the detection of prostate cancer lesions. Pdf prostatespecific membrane antigen as a target for.
Prostatespecific membrane antigen targeted protein contrast. Cancer targeted technology highlights prostate cancer pet. Prostatespecific membrane antigen targeted imaging and therapy of prostate cancer using a psma inhibitor as a homing ligand article in molecular pharmaceutics 63. Chimeric antigen receptor car t cell therapy for hematologic malignancies is fraught with several unknowns, including number of functional t cells that engage target tumor, durability and subsequent expansion and contraction of that engagement, and whether toxicity can be managed. Controversies with psmabased imaging and targeted therapy. Small molecule psma inhibitors labeled with 177 lu lutetium177 or 1 i show promise for treatment of prostate cancer. To assess the ability of nns1,3dicarboxypropylcarbamoyl4ffluorobenzyllcysteine fdcfbc, a prostatespecific membrane antigentargeted pet agent, to detect localized prostate cancer lesions in correlation with multiparametric mri mpmri and histopathology. Prostascint is an fda approved imaging agent for prostate cancer. Prostate specific membrane antigen psma, is a unique membrane bound glycoprotein, which is overexpressed manifold on prostate cancer as well as neovasculature of most of the solid tumors, but not in the vasculature of the normal tissues.
In this study, we evaluate the potential of prostate specific membrane antigen psma as target for radioligand therapy rlt. Early detection is a major challenge for all conventional imaging modalities. Prostate specific membrane antigena target for imaging and. Proposal for a structured reporting system for prostate. Prostatespecific membrane antigen targeted imaging and therapy of prostate cancer using a psma inhibitor as a homing ligand sumith a. The psma ligand labeled with a positron emitter like 68ga18f helps not only to select patients. Auger radiopharmaceutical therapy targeting prostatespecific. Technology prostate specific membrane antigen psma. Biodistribution and radiation dosimetry for a probe. Key issues for prostate cancer patients are the detection of recurrent disease and the treatment of metastasized cancer. Additionally, one of the common characteristics of many solid tumors, such as prostate cancer, is hypoxia. Prostate cancer radiotherapy more precisely targeted with. Because the prostate specific membrane antigen psma is frequently overexpressed in. Blue earth diagnostics announces dosing of first patient.
In recent years, smallmolecule inhibitors of prostate specific membrane antigen psma labeled with radionuclides that allow for positron emission tomography pet imaging have been extensively studied in many clinical contexts in men with prostate cancer pca. In addition, increased psma expression correlates with castration resistance and progression to the metastatic stage of the disease. April 24, 2017 cancer targeted technology recently announced it is focusing on small molecules that target pivotal enzyme targets on cancer. Recent observations reveal that the microvascular endothelium of primary highgrade gliomas expresses psma. Prostatespecific membrane antigen targeted imaging and therapy. Docetaxel is a food and drug administrationapproved drug for treating metastatic and androgenindependent prostate cancer, and mocetinostat is a potent inhibitor of class i histone deacetylases.
Pdf biodistribution and radiation dosimetry for a probe. The rapidly expanding clinical adaptation of prostatespecific membrane antigen psma targeted pet imaging in the evaluation of patients with prostate cancer has placed an increasing onus on understanding both the potential pearls of. Prostate specific membrane antigen psma is one of the most specific cell surface markers for prostate cancer diagnosis and targeted treatment. Prostate specific membrane antigen psmabased pet imaging of high risk prostate cancer the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Auger radiopharmaceutical therapy targeting prostate specific membrane antigen.
Prostate specific membrane antigen psma is a membrane protein that is overexpressed manifold in prostate cancer and provides an attractive target for molecular therapy. Triplenegative breast cancer has extremely high risk of relapse due to the lack of targeted therapies, intra and intertumoral heterogeneity, and the inherent and acquired resistance to therapies. However, it may be a valuable tool for detecting metastatic lymph nodes, distant metastasis and recurrent hcc. In this study, we evaluate the potential of prostatespecific membrane antigen psma as target for radioligand therapy rlt. Progenics molecular imaging radiopharmaceutical product candidate 1404 targets the extracellular domain of prostate specific membrane antigen psma, a protein amplified on the surface of 95% of prostate cancer cells and a validated target for the detection of primary and metastatic prostate cancer. A dextranbased probe for the targeted magnetic resonance.
Development of prostate specific membrane antigen targeted. The companys pipeline includes innovative prostate specific membrane antigen psma targeted radiohybrid rh agents, which are a clinicalstage, investigational class of theranostic compounds, with potential applications in both the imaging and treatment of prostate cancer. Second generation 18flabeled prostatespecific membrane. Prostatespecific membrane antigen targeted polymersomes. Kiess ap, minn i, chen y, hobbs r, sgouros g, mease rc. The prostate specific membrane antigen psma is a molecular target whose use has resulted in some of the most productive work toward imaging and treating prostate cancer over the past two decades. Biodistribution and radiation dosimetry for a probe targeting. Statistical analysis was performed using a t test microsoft excel software. A prostatespecific membrane antigentargeted monoclonal.
Prostatespecific membrane antigen psma is a type ii integral membrane protein with expression within normal prostate and overexpression on the surface of prostate cancer cells 1011. Recent developments in pca targeted radiopharmaceuticals have focused on prostate specific membrane antigen psma ligands. Prostate specific membrane antigen psma is typically highly expressed in prostate cancer, and the gluurealys gul structure has recently received considerable attention as a key unit of psmatargeting agents. To assess the ability of nns1,3dicarboxypropyl carbamoyl 4ffluorobenzyllcysteine fdcfbc, a prostatespecific membrane antigentargeted pet agent, to detect localized prostate cancer lesions in correlation with multiparametric mri mpmri and histopathology. Mln2704 is an antibodychemotherapeutic conjugate designed to target prostate specific membrane antigen psma. Ctt develops small molecule scaffolds with a unique mode of binding to enzyme biomarkers important in cancer. Psma can be labeled with 68 ga and 18 f for imaging purposes. Prostate cancer radiotherapy more precisely targeted with nuclear medicine imaging. Targeted prostate biopsy using 68 gallium psmapetct for.
Prostatespecific membrane antigentargeted sitedirected. The high sensitivity and specificity of these agents for identifying sites of pca has quickly led to their widespread adoption as a. Evidence of prostatespecific membrane antigen expression. Among the wide array of molecular agents that have been developed for imaging prostate cancer pca, perhaps the most exciting results have been generated with the ureabased small molecules targeting the active site of prostatespecific membrane antigen psma 79. Glutamate carboxypeptidase ii gcpii, also known as nacetyllaspartyllglutamate peptidase i naaladase i, naag peptidase, or prostate specific membrane antigen psma is an enzyme that in humans is encoded by the folh1 folate hydrolase 1 gene. Correlation with multiparametric mri and histopathology. Oct 22, 2019 triplenegative breast cancer has extremely high risk of relapse due to the lack of targeted therapies, intra and intertumoral heterogeneity, and the inherent and acquired resistance to therapies. Nearinfrared photoimmunotherapy targeting prostate cancer.
Listing a study does not mean it has been evaluated by the u. Evaluation of novel prostatespecific membrane antigen. Lymph nodes are the second most common site of metastases in prostate cancer. Prostate specific membrane antigen targeted 18fdcfpyl.
Prostate specific membrane antigen targeted radiotracers are promising agents for imaging patients with prostate cancer biochemical recurrence after. Using a ligand targeting, the prostatespecific membrane antigen psma, which is overexpressed in a majority of prostate cancer pca cells, enables effective molecular imaging and targeted radioligand therapy of pca, with acceptable toxicity. Initial evaluation of 18 fdcfpyl for prostatespecific. Tube formation was investigated after incubation of endothelial huvec. Prostatespecific membrane antigenbased imaging sciencedirect. From the molecular imaging program, national cancer institute, bethesda. Among them, methyl cysteineglutamate urea mcg has been successfully labeled with both fluorescent dyes and radioisotopes for prostate cancer imaging. Imaging prostate cancer with prostatespecific membrane. Assessment of an 18flabeled phosphoramidate peptidomimetic. However, achieving molecular imaging using noninvasive mri with high resolution has yet to be achieved due to the lack of contrast agents with significantly improv nanoscale approaches for cancer diagnosis and treatment. As the first step in validating the applicability of prostatespecific membrane antigen psmatargeted imaging in highgrade gliomas, we evaluated the ability of the psma targeted small molecule 18 fdcfpyl 231carboxy56 18 ffluoropyridine3carbonylaminopentylureidopentanedioic acid to image highgrade gliomas in a series of 3 prospectively recruited patients. Ctts theranostic program is focused on the development of two drugs, ctt1057 and ctt1403, that respectively diagnose and treat prostate cancer based on targeting the biomarker prostatespecific membrane antigen psma. Because psma levels are directly related to androgen independence, metastasis and progression, psma could prove an important target for the development of new radiopharmaceuticals for pet. Prostate specific membrane antigen psma is a promising target for diagnosis and treatment of prostate cancer.
Pet imaging of prostatespecific membrane antigen in prostate. In recent years, smallmolecule inhibitors of prostatespecific membrane antigen psma labeled with radionuclides that allow for positron emission tomography pet imaging have been extensively studied in many clinical contexts in men with prostate cancer pca. A novel 111inlabeled antiprostatespecific membrane. Furthermore, therapy of patients with hormoneresistant tumor lesions presents a major clinical challenge. For imagej analysis, wholebody imaging was acquired in gray scale and processed in imagej software.
Psma is a transmembrane receptor whose expression is largely restricted to prostatic epithelium and prostate cancer cells with its expression level increasing during the progression of malignancy. Wholebody distribution and radiation dosimetry of this new probe were evaluated. An improved prostate specific membrane antigen targeting. Because the prostatespecific membrane antigen psma is frequently overexpressed in. It is an excellent target for imaging cancer 10, particularly prostate cancer, because of its limited expression in normal nonmalignant tissues. Prostatespecific membrane antigen as a target several biologic characteristics make prostatespecific membrane antigen psma, also known as folate hydrolase i or glutamate carboxypeptidase ii, an outstanding target for drug development.
Preclinical dosimetry, imaging, and targeted radionuclide. Prostatespecific membrane antigen psma continues to be the hallmark biomarker for prostate cancer as it is expressed on nearly all prostatic tumors. Prostatespecific membrane antigen targeted imaging and therapy of prostate cancer using a psma inhibitor as a homing ligand. Salas fragomeni ra 1, menke jr, holdhoff m, ferrigno c, laterra jj, solnes lb, javadi ms, szabo z, pomper mg, rowe sp. Purpose to assess the ability of nns1,3dicarboxypropylcarbamoyl418 ffluorobenzyllcysteine 18 fdcfbc, a prostate specific membrane antigen targeted pet agent, to detect localized prostate cancer lesions in correlation with multiparametric mri mpmri and histopathology. Prostatespecific membrane antigen psma is a promising target for diagnosis and treatment of prostate cancer. Targeted, activatable, in vivo fluorescence imaging of. Prostate specific membrane antigen imaging psma prostate specific membrane antigen or psma imaging is a nuclear medicine exam using positron emission tomography pet to detect prostate cancer. We developed a prostate specific membrane antigen psma targeted nearinfrared nir imaging agent otl78 that. Prostatespecific membrane antigentargeted imaging with 18f dcfpyl in highgrade gliomas. Here we present initial safety, biodistribution, and radiation dosimetry results with 18 fdcfpyl, a secondgeneration fluorine18labeled smallmolecule psma inhibitor, in patients with prostate cancer. Targeting the psma receptor creates a unique opportunity for drug delivery. Evaluation of novel prostatespecific membrane antigentargeted. Prostate specific membrane antigen psma targeted microbubbles.
Prostatespecific membrane antigen targeted imaging and. In the last several years, pca imaging probes targeting psma have been developed in academia as well as in industry. Prostate cancertargeted apodox retained the high potency of dox in attenuation. Results of a prospective, phase ii, single center study. Methods in the present study, an irreversible phosphoramidate inhibitor, ctt.
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