Novel Preclinical and Radiopharmaceutical Aspects of [68Ga]Ga-PSMA-HBED-CC: A New PET Tracer for Imaging of Prostate Cancer
Matthias Eder1,2, Oliver Neels1,2, Miriam Müller1, Ulrike Bauder-Wüst1, Yvonne Remde1, Martin Schäfer1, Ute Hennrich1,2, Michael Eisenhut1, Ali Afshar-Oromieh3, Uwe Haberkorn3 and Klaus Kopka1,2
1German Cancer Research Center (dkfz), Division of Radiopharmaceutical Chemistry, Im Neuenheimer Feld 280, Heidelberg 69120, Germany, 2German Cancer Consortium (DKTK), Im Neuenheimer Feld 280, Heidelberg 69120, Germany,3Department of Nuclear Medicine, University of Heidelberg, Im Neuenheimer Feld 400, Heidelberg 69120, Germany
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 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.
For Open Access Article, see: Eder, M.; Neels, O.; Müller, M.; Bauder-Wüst, U.; Remde, Y.; Schäfer, M.; Hennrich, U.; Eisenhut, M.; Afshar-Oromieh, A.; Haberkorn, U.; Kopka, K. Novel Preclinical and Radiopharmaceutical Aspects of [68Ga]Ga-PSMA-HBED-CC: A New PET Tracer for Imaging of Prostate Cancer. Pharmaceuticals 2014, 7, 779-796.
Endocrine Disorders in Childhood Cancer Survivors Treated with Haemopoietic Stem Cell Transplantation
Christina Wei1 and Assunta Albanese1,2
1St Georges Hospital, St Georges Health Care NHS Trust, Tooting, London SW17 0QT, UK, 2Royal Marsden Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, UK
Abstract: The increasing number of haemopoietic stem cell transplantations (HSCT) taking place worldwide has offered a cure to many high risk childhood malignancies with an otherwise very poor prognosis. However, HSCT is associated with an increased risk of morbidity and premature death, and patients who have survived the acute complications continue to face lifelong health sequelae as a result of the treatment. Endocrine dysfunction is well described in childhood HSCT survivors treated for malignancies. The endocrine system is highly susceptible to damage from the conditioning therapy, such as, alkylating agents and total body irradiation, which is given prior stem cell infusion. Although not immediately life-threatening, the impact of these abnormalities on the long term health and quality of life in these patients may be considerable. The prevalence, risk factors, clinical approaches to investigations and treatments, as well as the implications of ongoing surveillance of endocrine disorders in childhood HSCT survivors, are discussed in this review.
For Open Access Article, see: Wei, C.; Albanese, A. Endocrine Disorders in Childhood Cancer Survivors Treated with Haemopoietic Stem Cell Transplantation. Children 2014, 1, 48-62.
Roles of Matrix Metalloproteinases and Their Natural Inhibitors in Prostate Cancer Progression
Yixuan Gong, Uma D. Chippada-Venkata and William K. Oh
Division of Hematology and Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Abstract: Matrix metalloproteinases (MMPs), a group of zinc-dependent endopeptidases involved in the degradation of the extracellular matrix, play an important role in tissue remodeling associated with various physiological processes such as morphogenesis, angiogenesis, and tissue repair, as well as pathological processes including cirrhosis, arthritis and cancer. The MMPs are well established as mediators of tumor invasion and metastasis by breaking down connective tissue barriers. Although there has been a vast amount of literature on the role of MMPs in invasion, metastasis and angiogenesis of various cancers, the role of these endopeptidases in prostate cancer progression has not been systematically reviewed. This overview summarizes findings on the tissue and blood expression of MMPs, their function, regulation and prognostic implication in human prostate cancer, with a focus on MMP-2, -7, -9, MT1-MMP and tissue inhibitor of metalloproteinase 1 (TIMP-1). This review also summarizes the efficacy and failure of early-generation matrix metalloproteinase inhibitors (MMPIs) in the treatment of metastatic prostate cancer and highlights the lessons and challenges for next generation MMPIs.
For Open Access Article, see: Gong, Y.; Chippada-Venkata, U.D.; Oh, W.K. Roles of Matrix Metalloproteinases and Their Natural Inhibitors in Prostate Cancer Progression. Cancers 2014, 6, 1298-1327.
Merkel Cell Polyomavirus: Molecular Insights into the Most Recently Discovered Human Tumour Virus
Gabrielė Stakaitytė, Jennifer J. Wood, Laura M. Knight, Hussein Abdul-Sada, Noor Suhana Adzahar, Nnenna Nwogu, Andrew Macdonald and Adrian Whitehouse
School of Molecular and Cellular Biology and Astbury Centre of Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK
Abstract: A fifth of worldwide cancer cases have an infectious origin, with viral infection being the foremost. One such cancer is Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy. In 2008, Merkel cell polyomavirus (MCPyV) was discovered as the causative agent of MCC. It is found clonally integrated into the majority of MCC tumours, which require MCPyV oncoproteins to survive. Since its discovery, research has begun to reveal the molecular virology of MCPyV, as well as how it induces tumourigenesis. It is thought to be a common skin commensal, found at low levels in healthy individuals. Upon loss of immunosurveillance, MCPyV reactivates, and a heavy viral load is associated with MCC pathogenesis. Although MCPyV is in many ways similar to classical oncogenic polyomaviruses, such as SV40, subtle differences are beginning to emerge. These unique features highlight the singular position MCPyV has as the only human oncogenic polyomavirus, and open up new avenues for therapies against MCC.
For Open Access Article, see: Stakaitytė, G.; Wood, J.J.; Knight, L.M.; Abdul-Sada, H.; Adzahar, N.S.; Nwogu, N.; Macdonald, A.; Whitehouse, A. Merkel Cell Polyomavirus: Molecular Insights into the Most Recently Discovered Human Tumour Virus. Cancers 2014, 6, 1267-1297.