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Pharmaceuticals, Volume 7, Issue 7 (July 2014) – 5 articles , Pages 754-849

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Editorial
Pharmaceuticals—Special Issue on Radiopharmaceutical Chemistry between Imaging and Endoradiotherapy
Pharmaceuticals 2014, 7(7), 839-849; https://doi.org/10.3390/ph7070839 - 16 Jul 2014
Cited by 1 | Viewed by 4329
Abstract
The fields of molecular biology, immunology and genetics have generated many important developments that advance the understanding of the induction and progression of oncological, cardiological and neurological diseases as well as the identification of disease-associated molecules and drugs that specifically target diseased cells [...] Read more.
The fields of molecular biology, immunology and genetics have generated many important developments that advance the understanding of the induction and progression of oncological, cardiological and neurological diseases as well as the identification of disease-associated molecules and drugs that specifically target diseased cells during therapy. These insights have triggered the development of targeted radiopharmaceuticals which open up a new dimension of radiopharmaceutical sciences in nuclear medicine. Radiopharmaceuticals, also called radiotracers, are radiolabelled molecules, bearing a “radioactive lantern”, and used as molecular probes to address clinically relevant biological targets such as receptors, enzymes, transport systems and others. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) realised in the en-vogue hybrid technologies PET/CT, SPECT/CT and PET/MRI represent the state-of-the-art diagnostic imaging technologies in nuclear medicine which are used to follow the trace of the administered radiopharmaceutical noninvasively thereby in vivo visualising and assessing biological processes at the subcellular and molecular level in a highly sensitive manner. In this connexion novel radiopharmaceuticals for the noninvasive molecular imaging of early disease states and monitoring of treatment responses in vivo by means of PET/CT, SPECT/CT and PET/MRI are indispensable prerequisites to further advance and strengthen the unique competence of radiopharmaceutical sciences. In the era of personalised medicine the diagnostic potential of radiopharmaceuticals is directly linked to a subsequent individual therapeutic approach called endoradiotherapy. Depending on the “radioactive lantern” (gamma or particle emitter) used for radiolabelling of the respective tracer molecule, the field of Radiopharmaceutical Chemistry can contribute to the set-up of an “in vivo theranostic” approach especially in tumour patients by offering tailor-made (radio)chemical entities labelled either with a diagnostic or a therapeutic radionuclide. [...] Full article
(This article belongs to the Special Issue Radiopharmaceutical Chemistry between Imaging and Radioendotherapy)
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Review
The Medicinal Chemistry of Imidazotetrazine Prodrugs
Pharmaceuticals 2014, 7(7), 797-838; https://doi.org/10.3390/ph7070797 - 10 Jul 2014
Cited by 29 | Viewed by 5598
Abstract
Temozolomide (TMZ) is the standard first line treatment for malignant glioma, reaching “blockbuster” status in 2010, yet it remains the only drug in its class. The main constraints on the clinical effectiveness of TMZ therapy are its requirement for active DNA mismatch repair [...] Read more.
Temozolomide (TMZ) is the standard first line treatment for malignant glioma, reaching “blockbuster” status in 2010, yet it remains the only drug in its class. The main constraints on the clinical effectiveness of TMZ therapy are its requirement for active DNA mismatch repair (MMR) proteins for activity, and inherent resistance through O6-methyl guanine-DNA methyl transferase (MGMT) activity. Moreover, acquired resistance, due to MMR mutation, results in aggressive TMZ-resistant tumour regrowth following good initial responses. Much of the attraction in TMZ as a drug lies in its PK/PD properties: it is acid stable and has 100% oral bioavailability; it also has excellent distribution properties, crosses the blood-brain barrier, and there is direct evidence of tumour localisation. This review seeks to unravel some of the mysteries of the imidazotetrazine class of compounds to which TMZ belongs. In addition to an overview of different synthetic strategies, we explore the somewhat unusual chemical reactivity of the imidazotetrazines, probing their mechanisms of reaction, examining which attributes are required for an active drug molecule and reviewing the use of this combined knowledge towards the development of new and improved anti-cancer agents. Full article
(This article belongs to the Special Issue Prodrugs: from Design to Clinic)
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Article
Novel Preclinical and Radiopharmaceutical Aspects of [68Ga]Ga-PSMA-HBED-CC: A New PET Tracer for Imaging of Prostate Cancer
Pharmaceuticals 2014, 7(7), 779-796; https://doi.org/10.3390/ph7070779 - 30 Jun 2014
Cited by 259 | Viewed by 10966
Abstract
The detection of prostate cancer lesions by PET imaging of the prostate-specific membrane antigen (PSMA) has gained highest clinical impact during the last years. 68Ga-labelled Glu-urea-Lys(Ahx)-HBED-CC ([68Ga]Ga-PSMA-HBED-CC) represents a successful novel PSMA inhibitor radiotracer which has recently demonstrated its suitability [...] Read more.
The detection of prostate cancer lesions by PET imaging of the prostate-specific membrane antigen (PSMA) has gained highest clinical impact during the last years. 68Ga-labelled Glu-urea-Lys(Ahx)-HBED-CC ([68Ga]Ga-PSMA-HBED-CC) represents a successful novel PSMA inhibitor radiotracer which has recently demonstrated its suitability in individual first-in-man studies. The radiometal chelator HBED-CC used in this molecule represents a rather rarely used acyclic complexing agent with chemical characteristics favourably influencing the biological functionality of the PSMA inhibitor. The simple replacement of HBED-CC by the prominent radiometal chelator DOTA was shown to dramatically reduce the in vivo imaging quality of the respective 68Ga-labelled PSMA-targeted tracer proving that HBED-CC contributes intrinsically to the PSMA binding of the Glu-urea-Lys(Ahx) pharmacophore. Owing to the obvious growing clinical impact, this work aims to reflect the properties of HBED-CC as acyclic radiometal chelator and presents novel preclinical data and relevant aspects of the radiopharmaceutical production process of [68Ga]Ga-PSMA-HBED-CC. Full article
(This article belongs to the Special Issue Radiopharmaceutical Chemistry between Imaging and Radioendotherapy)
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Review
Imaging Biomarkers or Biomarker Imaging?
Pharmaceuticals 2014, 7(7), 765-778; https://doi.org/10.3390/ph7070765 - 25 Jun 2014
Cited by 11 | Viewed by 3659
Abstract
Since biomarker imaging is traditionally understood as imaging of molecular probes, we highly recommend to avoid any confusion with the previously defined term “imaging biomarkers” and, therefore, only use “molecular probe imaging (MPI)” in that context. Molecular probes (MPs) comprise all kinds of [...] Read more.
Since biomarker imaging is traditionally understood as imaging of molecular probes, we highly recommend to avoid any confusion with the previously defined term “imaging biomarkers” and, therefore, only use “molecular probe imaging (MPI)” in that context. Molecular probes (MPs) comprise all kinds of molecules administered to an organism which inherently carry a signalling moiety. This review highlights the basic concepts and differences of molecular probe imaging using specific biomarkers. In particular, PET radiopharmaceuticals are discussed in more detail. Specific radiochemical and radiopharmacological aspects as well as some legal issues are presented. Full article
(This article belongs to the Special Issue Radiopharmaceutical Chemistry between Imaging and Radioendotherapy)
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Article
Correlation between the Serum Pepsinogen I Level and the Symptom Degree in Proton Pump Inhibitor-Users Administered with a Probiotic
Pharmaceuticals 2014, 7(7), 754-764; https://doi.org/10.3390/ph7070754 - 25 Jun 2014
Cited by 7 | Viewed by 3614
Abstract
In patients with functional upper gastrointestinal disorders such as gastroesophageal reflux disease and functional dyspepsia, the presence of symptoms is thought to occur in the absence of any organic diseases and the mechanisms behind this remain unclear. We therefore examined the relationship between [...] Read more.
In patients with functional upper gastrointestinal disorders such as gastroesophageal reflux disease and functional dyspepsia, the presence of symptoms is thought to occur in the absence of any organic diseases and the mechanisms behind this remain unclear. We therefore examined the relationship between stomach-related biomarker levels and symptoms. Twenty-four outpatients who had taken proton-pump inhibitors every day were enrolled in this study. The subjects consumed yogurt containing 109 colony-forming units of Lactobacillus gasseri OLL2716 (LG21) every day for three months. They underwent four clinical examinations in total. Each examination consisted of answering a questionnaire with a frequency scale for the symptoms of GERD (FSSG), and included measurements of the serum gastrin, ghrelin, and pepsinogens I and II levels. As a result, the FSSG score and the PGI value showed a decrease and an increase, respectively, after LG21 treatment when analyzed without age adjustment. A multiple regression analysis with additional adjustments for gender and age revealed a strong association between the PGI value and the FSSG symptom scores. Therefore either the PGI level itself or the factors regulating the PGI level might be involved in the etiology of these symptoms. Full article
(This article belongs to the Special Issue Probiotics and Prebiotics 2015)
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