Chaperone Therapy in Fabry Disease Weidemann, Frank; Jovanovic, Ana; Herrmann, Ken ...
International journal of molecular sciences,
02/2022, Volume:
23, Issue:
3
Journal Article
Peer reviewed
Open access
Fabry disease is an X-linked lysosomal multisystem storage disorder induced by a mutation in the alpha-galactosidase A (GLA) gene. Reduced activity or deficiency of alpha-galactosidase A (AGAL) leads ...to escalating storage of intracellular globotriaosylceramide (GL-3) in numerous organs, including the kidneys, heart and nerve system. The established treatment for 20 years is intravenous enzyme replacement therapy. Lately, oral chaperone therapy was introduced and is a therapeutic alternative in patients with amenable mutations. Early starting of therapy is essential for long-term improvement. This review describes chaperone therapy in Fabry disease.
Prostate-specific membrane antigen (PSMA)-ligand PET imaging provides unprecedented accuracy for whole-body staging of prostate cancer. As PSMA-ligand PET/CT is increasingly adopted in clinical ...trials and routine practice worldwide, a unified language for image reporting is urgently needed. We propose a molecular imaging TNM system (miTNM, version 1.0) as a standardized reporting framework for PSMA-ligand PET/CT or PET/MRI. miTNM is designed to organize findings in comprehensible categories to promote the exchange of information among physicians and institutions. Additionally, flowcharts integrating findings of PSMA-ligand PET and morphologic imaging have been designed to guide image interpretation. Specific applications, such as assessment of prognosis or impact on management, should be evaluated in future trials. miTNM is a living framework that evolves with clinical experience and scientific data.
Radiotheranostics, injectable radiopharmaceuticals with antitumour effects, have seen rapid development over the past decade. Although some formulations are already approved for human use, more ...radiopharmaceuticals will enter clinical practice in the next 5 years, potentially introducing new therapeutic choices for patients. Despite these advances, several challenges remain, including logistics, supply chain, regulatory issues, and education and training. By highlighting active developments in the field, this Review aims to alert practitioners to the value of radiotheranostics and to outline a roadmap for future development. Multidisciplinary approaches in clinical trial design and therapeutic administration will become essential to the continued progress of this evolving therapeutic approach.
Rationale
The development of consensus guidelines for interpretation of Prostate-Specific Membrane Antigen (PSMA)-Positron Emission Tomography (PET) is needed to provide more consistent reports in ...clinical practice. The standardization of PSMA-PET interpretation may also contribute to increasing the data reproducibility within clinical trials. Finally, guidelines in PSMA-PET interpretation are needed to communicate the exact location of findings to referring physicians, to support clinician therapeutic management decisions.
Methods
A panel of worldwide experts in PSMA-PET was established. Panelists were selected based on their expertise and publication record in the diagnosis or treatment of PCa, in their involvement in clinical guidelines and according to their expertise in the clinical application of radiolabeled PSMA inhibitors. Panelists were actively involved in all stages of a modified, nonanonymous, Delphi consensus process.
Results
According to the findings obtained by modified Delphi consensus process, panelist recommendations were implemented in a structured report for PSMA-PET.
Conclusions
The E-PSMA standardized reporting guidelines, a document supported by the European Association of Nuclear Medicine (EANM), provide consensus statements among a panel of experts in PSMA-PET imaging, to develop a structured report for PSMA-PET in prostate cancer and to harmonize diagnostic interpretation criteria.
The aim of this guideline is to provide standards for the recommendation, performance, interpretation and reporting of
68
Ga-PSMA PET/CT for prostate cancer imaging. These recommendations will help ...to improve accuracy, precision, and repeatability of
68
Ga-PSMA PET/CT for prostate cancer essentially needed for implementation of this modality in science and routine clinical practice.
Intratumoral heterogeneity of signaling networks may contribute to targeted cancer therapy resistance, including in the highly lethal brain cancer glioblastoma (GBM). We performed single-cell ...phosphoproteomics on a patient-derived in vivo GBM model of mTOR kinase inhibitor resistance and coupled it to an analytical approach for detecting changes in signaling coordination. Alterations in the protein signaling coordination were resolved as early as 2.5 days after treatment, anticipating drug resistance long before it was clinically manifest. Combination therapies were identified that resulted in complete and sustained tumor suppression in vivo. This approach may identify actionable alterations in signal coordination that underlie adaptive resistance, which can be suppressed through combination drug therapy, including non-obvious drug combinations.
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•Sequencing excludes the selection of an mTORki-resistant genotype in a GBM model•Heterogeneous signaling networks rapidly adapt to mTORki to drive resistance•Resistance-promoting signaling is observed a priori by single-cell analysis•Network analyses point to therapy combinations for long-term disease suppression
Wei et al. utilize single-cell phosphoproteomic analysis of patient-derived glioblastoma models to identify shifts in signaling coordination following short-term treatment with kinase inhibitors, which facilitates the design of combination therapy approaches with reduced resistance and improved efficacy.
PSMA Ligands for PET Imaging of Prostate Cancer Schwarzenboeck, Sarah M; Rauscher, Isabel; Bluemel, Christina ...
The Journal of nuclear medicine (1978),
10/2017, Volume:
58, Issue:
10
Journal Article
Peer reviewed
Open access
Targeting the prostate-specific membrane antigen (PSMA) with
Ga-labeled and
F-labeled PET agents has become increasingly important in recent years. Imaging of biochemically recurrent prostate cancer ...has been established as a widely accepted clinical indication for PSMA ligand PET/CT in many parts of the world because of the results of multiple, primarily retrospective, studies that indicate superior detection efficacy compared with standard-of-care imaging. For high-risk primary prostate cancer, evidence is growing that this modality significantly aids in the detection of otherwise occult nodal and bone metastases. For both clinical indications in recurrent as well as in primary prostate cancer, preliminary data demonstrate a substantial impact on clinical management. Emerging data imply that intraprostatic tumor localization, therapy stratification, and treatment monitoring of advanced disease in specific clinical situations might become future indications. Current criteria for image reporting of PSMA ligand PET are evolving given the expanding body of literature on physiologic and pathologic uptake patterns and pitfalls. This article intends to give an educational overview on the current status of PSMA ligand PET imaging, including imaging procedure and interpretation, clinical indications, diagnostic potential, and impact on treatment planning.
Information has been collected from PET/MRI operational sites to identify its present and future applications. This may help to focus discussions on common interests of the PET/MRI community.
A ...web-based survey of PET/MRI users was conducted from June to October 2015. The survey was composed of 26 questions related to the PET/MRI center, present use and imaging protocols, and perspectives on key applications.
Responses were collected from 39 international sites that operated PET/MRI for a median of 30 mo (range, 2-62 mo). Most installations were located in public institutions with an academic focus (n = 26, 67%). Systems were primarily operated by nuclear medicine departments (n = 13, 33%), jointly by nuclear medicine and radiology (n = 11, 28%), and radiology only (n = 10, 26%). PET/MRI operation was equally focused on clinic routine and research (47% vs. 45% of sites, respectively). Sites reported a strong focus on oncology (76% of research and 88% of clinical applications). Other applications included neurology (9% clinical, 12% research) and cardiology (3% clinical, 6% research). Perceived superiority over PET/CT was identified as the strongest driver for clinical adoption. Over half the operators expect PET/MRI to excel in clinical routine within 3-5 y. Emerging key applications for future PET/MRI use were cardiovascular disease and imaging of inflammation.
An international survey of early PET/MR adopters reveals a mixed use of this combined imaging modality, with a focus on oncology. The future of PET/MRI is seen in expanded application for oncology and neurology, but also cardiovascular disease and inflammation.
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