Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.17.21 (prostate-specific membrane antigen)
 1,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is imperative that the thrust of clinical practice in the ensuing years would be to develop personalized management model for various disorders. PET-computed tomography (PET-CT) based molecular functional imaging has been increasingly utilized for assessment of tumor and other nonmalignant disorders and has the ability to explore disease phenotype on an individual basis and address critical clinical decision making questions related to practice of personalized medicine. Hence, it is essential to make a concerted systematic effort to explore and define the appropriate place of PET-CT in personalized clinical practice in each of malignancies, which would strengthen the concept further. The potential advantages of PET based disease management can be classified into broad categories: (1) Traditional: which includes assessment of disease extent such as initial disease staging and restaging, treatment response evaluation particularly early in the course and thus PET-CT response adaptive decision for continuing the same regimen or switching to salvage schedules; there has been continuous addition of newer application of PET based disease restaging in oncological parlance (eg, Richter transformation); (2) Recent and emerging developments: this includes exploring tumor biology with FDG and non-FDG PET tracers. The potential of multitracer PET imaging (particularly new and novel tracers, eg, 68Ga-DOTA-TOC/NOC/TATE in NET, 68Ga-PSMA and 18F-fluorocholine in prostate carcinoma, 18F-fluoroestradiol in breast carcinoma) has provided a scientific basis to stratify and select appropriate targeted therapies (both radionuclide and nonradionuclide treatment), a major boost for individualized disease management in clinical oncology. Integrating the molecular level information obtained from PET with structural imaging further individualizing treatment plan in radiation oncology, precision of interventions and biopsies of a particular lesion and forecasting disease prognosis.
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PMID:PET-Based Personalized Management in Clinical Oncology: An Unavoidable Path for the Foreseeable Future. 2732 Oct 25

Ga-68-labeled radiotracers, particularly used for the detection of neuroendocrine tumors by means of Ga-68-DOTA-TATE or -DOTA-TOC or for the diagnosis of prostate cancer by means of Ga-68-labeled antigens (Ga 68-PSMA), become increasingly important. In addition to the high sensitivity and specificity of these radiopharmaceuticals, the short-lived radionuclide Ga-68 offers almost ideal nuclear characteristics for use in PET. Ga-68 is obtained from a germanium-gallium-generator system, so that the availability of Ga-68-labeled radiotracers is independent of an on-site-cyclotron regardless of the short half-life of Ga-68 of about 68minutes. Regarding the disposal of the radioactively contaminated waste from the preparation of the radiopharmaceutical, the eluted Ga-68 has to be considered to be additionally contaminated with its parent nuclide Ge-68. Due to this production-related impurity in combination with the short half-life of Ga-68, the radioactive waste has to be considered to be contaminated with Ge-68 and Ga-68 in radioactive equilibrium (hereafter referred to as Ge-68+). As there are no clearance levels for Ge-68+ given in the German Radiation Protection Ordinance, this work presents a method to calculate the missing value basing on a recommendation of the German Radiation Protection Commission in combination with simple geometric models of practical radiation protection. Regarding the relevant exposure scenarios, a limit value for the unrestricted clearance of Ge-68+ of 0.4 Bq/g was determined.
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PMID:[Disposal of radioactive contaminated waste from Ga-68-PET - calculation of a clearance level for Ge-68]. 2743 73

Radiopharmaceuticals used for diagnosis or therapy induce DNA strand breaks, which may be detectable by single-cell gel electrophoresis (called comet assay). Blood was taken from patients before and at different time points after treatment with radiopharmaceuticals; blood cells were investigated by the comet assay using the percentage of DNA in the tail as the critical parameter. Whereas [225Ac]Ac-prostate-specific membrane antigen (PSMA)-617 alpha therapy showed no difference relative to the blood sample taken before treatment, beta therapy with [177Lu]Lu-PSMA-617 3 h post-injection revealed a small but significant increase in DNA strand breaks. In blood of patients who underwent positron emission tomography (PET) with either [18F]2-fluor-2-deoxy-D-glucose (FDG) or [68Ga]Ga-PSMA-11, an increase of DNA migration determined by the comet assay was not found when analysed at different time points (2-70 min) after intravenous tracer injection. Human whole blood was incubated with the targeted clinically relevant therapeutic radiopharmaceuticals [225Ac]Ac-PSMA-617, [177Lu]Lu-PSMA-617 and [90Y]Y-DOTA(0)-Phe(1)-Tyr(3)-octreotide (DOTA-TOC) at different activity concentrations (kBq/ml) for 5 days and then analysed by the comet assay. DNA damage increased with higher concentrations of all radiolabeled compounds tested. [177Lu]Lu-PSMA-617 caused higher blood cell radiotoxicity than equal activity concentrations of [90Y]Y-DOTA-TOC. Likewise, whole human blood was exposed to the positron emitters [18F]FDG and [68Ga]Ga-PSMA-11 in vitro for 24 h with activity concentrations ranging between 5 and 40 MBq/ml. The same activity concentration dependent elevated DNA migration was observed for both compounds although decay energies are different. This study demonstrated that the amount of DNA damage detected by the comet assay in whole human blood is similar among different positron emitters and divergent by a factor of 200 between alpha particles and beta radiation.
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PMID:DNA damage in human whole blood caused by radiopharmaceuticals evaluated by the comet assay. 3110 37

A critical factor for clinical practice is the production of 68 Ga radiopharmaceuticals manufactured manually or through an automated procedure. 68 Ga radiopharmaceuticals are often prepared manually, although this method can lead to an increased operator's radiation dose and potential variability within production. The present work compares 68 Ga-radiolabelling (PSMA-11; DOTA-TOC) utilizing a cassette module (GAIA; Elysia-Raytest; Germany) with a manual setup for routine clinical production with regard to process reliability and reproducibility.
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PMID:Manual vs automated 68 Ga-radiolabelling-A comparison of optimized processes. 3184 8

Pancreatic neuroendocrine neoplasms (panNENs) are heterogeneous neoplasms with neuroendocrine differentiation that show peculiar clinical and histomorphological features, with variable prognosis. In recent years, advances in knowledge regarding the pathophysiology and heterogeneous clinical presentation, as well as the availability of different diagnostic procedures for panNEN diagnosis and novel therapeutic options for patient clinical management, has led to the recognition of the need for an active multidisciplinary discussion for optimal patient care. Molecular imaging with positron emission tomography/computed tomography (PET/CT) has become indispensable for the management of panNENs. Several PET radiopharmaceuticals can be used to characterize either panNEN receptor expression or metabolism. The aim of this review is to offer an overview of all the currently used radiopharmaceuticals and of the new upcoming tracers for pancreatic neuroendocrine tumors (panNETs), and their clinical impact on therapy management. [68Ga]Ga-DOTA-peptide PET/CT (SSA-PET/CT) has high sensitivity, specificity, and accuracy and is recommended for the staging and restaging of any non-insulinoma well-differentiated panNEN cases to carry out detection of unknown primary tumor sites or early relapse and for evaluation of in vivo somatostatin receptors expression (SRE) to select patient candidates for peptide receptor radiometabolic treatment (PRRT) with 90Y or 177Lu and/or cold analogs. SSA-PET/CT also has a strong impact on clinical management, leading to a change in treatment in approximately a third of the cases. Its role for treatment response assessment is still under debate due to the lack of standardized criteria, even though some semiquantitative parameters seem to be able to predict response. [18F]FDG PET/CT generally shows low sensitivity in small growing and well-differentiated neuroendocrine tumors (NET; G1 and G2), while it is of utmost importance in the evaluation and management of high-grade NENs and also provides important prognostic information. When positive, [18F]FDG PET/CT impacts therapeutical management, indicating the need for a more aggressive treatment regime. Although FDG positivity does not exclude the patient from PRRT, several studies have demonstrated that it is certainly useful to predict response, even in this setting. The role of [18F]FDOPA for the study of panNET is limited by physiological uptake in the pancreas and is therefore not recommended. Moreover, it provides no information on SRE that has crucial clinical management relevance. Early acquisition of the abdomen and premedication with carbidopa may be useful to increase the accuracy, but further studies are needed to clarify its utility. GLP-1R agonists, such as exendin-4, are particularly useful for benign insulinoma detection, but their accuracy decreases in the case of malignant insulinomas. Being a whole-body imaging technique, exendin-PET/CT gives important preoperative information on tumor size and localization, which is fundamental for surgical planning as resection (enucleation of the lesion or partial pancreatic resection) is the only curative treatment. New upcoming tracers are under study, such as promising SSTR antagonists, which show a favorable biodistribution and higher tumor-to-background ratio that increases tumor detection, especially in the liver. [68Ga]pentixafor, an in vivo marker of CXCR4 expression associated with the behavior of more aggressive tumors, seems to only play a limited role in detecting well-differentiated NET since there is an inverse expression of SSTR2 and CXCR4 in G1 to G3 NETs with an elevation in CXCR4 and a decrease in SSTR2 expression with increasing grade. Other tracers, such as [68Ga]Ga-PSMA, [68Ga]Ga-DATA-TOC, [18F]SiTATE, and [18F]AlF-OC, are also under investigation.
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PMID:Role of PET/CT and Therapy Management of Pancreatic Neuroendocrine Tumors. 3329 81