The purpose of the EANM Dosimetry Committee is to provide recommendations and guidance to scientists and clinicians on patient-specific dosimetry. Radiopharmaceuticals labelled with lutetium-177 ...(177Lu) are increasingly used for therapeutic applications, in particular for the treatment of metastatic neuroendocrine tumours using ligands for somatostatin receptors and prostate adenocarcinoma with small-molecule PSMA-targeting ligands. This paper provides an overview of reported dosimetry data for these therapies and summarises current knowledge about radiation-induced side effects on normal tissues and dose-effect relationships for tumours. Dosimetry methods and data are summarised for kidneys, bone marrow, salivary glands, lacrimal glands, pituitary glands, tumours, and the skin in case of radiopharmaceutical extravasation. Where applicable, taking into account the present status of the field and recent evidence in the literature, guidance is provided. The purpose of these recommendations is to encourage the practice of patient-specific dosimetry in therapy with 177Lu-labelled compounds. The proposed methods should be within the scope of centres offering therapy with 177Lu-labelled ligands for somatostatin receptors or small-molecule PSMA.
EANM practice guideline for quantitative SPECT-CT Dickson, John C.; Armstrong, Ian S.; Gabiña, Pablo Minguez ...
European journal of nuclear medicine and molecular imaging,
03/2023, Letnik:
50, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Purpose
Quantitative SPECT-CT is a modality of growing importance with initial developments in post radionuclide therapy dosimetry, and more recent expansion into bone, cardiac and brain imaging ...together with the concept of theranostics more generally. The aim of this document is to provide guidelines for nuclear medicine departments setting up and developing their quantitative SPECT-CT service with guidance on protocols, harmonisation and clinical use cases.
Methods
These practice guidelines were written by members of the European Association of Nuclear Medicine Physics, Dosimetry, Oncology and Bone committees representing the current major stakeholders in Quantitative SPECT-CT. The guidelines have also been reviewed and approved by all EANM committees and have been endorsed by the European Association of Nuclear Medicine.
Conclusion
The present practice guidelines will help practitioners, scientists and researchers perform high-quality quantitative SPECT-CT and will provide a framework for the continuing development of quantitative SPECT-CT as an established modality.
Assembly of protein complexes is considered a posttranslational process involving random collision of subunits. We show that within the Escherichia coli cytosol, bacterial luciferase subunits LuxA ...and LuxB assemble into complexes close to the site of subunit synthesis. Assembly efficiency decreases markedly if subunits are synthesized on separate messenger RNAs from genes integrated at distant chromosomal sites. Subunit assembly initiates cotranslationally on nascent LuxB in vivo. The ribosome-associated chaperone trigger factor delays the onset of cotranslational interactions until the LuxB dimer interface is fully exposed. Protein assembly is thus directly coupled to the translation process and involves spatially confined, actively chaperoned cotranslational subunit interactions. Bacterial gene organization into operons therefore reflects a fundamental cotranslational mechanism for spatial and temporal regulation that is vital to effective assembly of protein complexes.
•The first Symposium on Molecular Radiotherapy Dosimetry: the future of theragnostic was organised in Athens in Nov 2023.•Initially planned for 110 attendees, an larger facility had to be found to ...welcome 180 participants.•Several abstracts (80) were submitted, and 48 accepted as oral, 30 as electronic posters.•Eight sessions were organised (with invited speakers and oral presentations), 3 ePoster sessions, a specific sponsor session, 2 CPD sessions and a round table associating physicists, physicians, patient representatives took place during that very busy meeting.•A specific session was organised to present the newly published EFOMP Policy Statement 19: Dosimetry in nuclear medicine therapy – Molecular radiotherapy.•The event was considered a great success and is likely to become the first of a series.
The EFOMP Special Interest Group for Radionuclide Internal Dosimetry (SIG_FRID) organised its first scientific meeting, the Symposium on Molecular Radiotherapy Dosimetry, in Athens on November 9th–11th 2023. The Symposium was hosted by the Hellenic Association of Medical Physicists and the National and Kapodistrian University of Athens. This meeting gathered more than 180 scientists from 28 countries. Scientific, clinical and regulatory aspects were addressed by 8 invited experts. Two continuous professional development sessions were organised. A special round table gathering medical physics experts, physicians regulatory authority experts and patient representatives addressed the possibilities to increase clinical dosimetry dissemination. The event was supported by companies and a specific industry session allowed sponsors to present their products, innovations and future perspective in this field.
Dosimetry can be a useful tool for personalization of molecular radiotherapy (MRT) procedures, enabling the continuous development of theranostic concepts. However, the additional resource ...requirements are often seen as a barrier to implementation. This guide discusses the requirements for dosimetry and demonstrates how a dosimetry regimen can be tailored to the available facilities of a centre. The aim is to help centres wishing to initiate a dosimetry service but may not have the experience or resources of some of the more established therapy and dosimetry centres. The multidisciplinary approach and different personnel requirements are discussed and key equipment reviewed example protocols demonstrating these factors are given in the supplementary material for the main therapies carried out in nuclear medicine, including
131
I-NaI for benign thyroid disorders,
177
Lu-DOTATATE and
131
I-mIBG for neuroendocrine tumours and
90
Y-microspheres for unresectable hepatic carcinoma.
Various post‐translational modifications (PTMs) fine‐tune the functions of almost all eukaryotic proteins, and co‐regulation of different types of PTMs has been shown within and between a number of ...proteins. Aiming at a more global view of the interplay between PTM types, we collected modifications for 13 frequent PTM types in 8 eukaryotes, compared their speed of evolution and developed a method for measuring PTM co‐evolution within proteins based on the co‐occurrence of sites across eukaryotes. As many sites are still to be discovered, this is a considerable underestimate, yet, assuming that most co‐evolving PTMs are functionally associated, we found that PTM types are vastly interconnected, forming a global network that comprise in human alone >50 000 residues in about 6000 proteins. We predict substantial PTM type interplay in secreted and membrane‐associated proteins and in the context of particular protein domains and short‐linear motifs. The global network of co‐evolving PTM types implies a complex and intertwined post‐translational regulation landscape that is likely to regulate multiple functional states of many if not all eukaryotic proteins.
This study is the first large‐scale comparative analysis of multiple types of post‐translational modifications in different eukaryotic species. The resulting network of co‐evolving and functionally associated modifications reveals the global landscape of post‐translational regulation.
Synopsis
This study is the first large‐scale comparative analysis of multiple types of post‐translational modifications in different eukaryotic species. The resulting network of co‐evolving and functionally associated modifications reveals the global landscape of post‐translational regulation.
In all, 115 149 non‐redundant post‐translational modifications (PTMs) of 13 different types were collected from 8 eukaryotes.
Comparison of evolution speed reveals that carboxylation is the most conserved while SUMOylation is the fastest evolving PTM type.
Co‐evolution of PTM pairs that co‐occur within proteins reveals a vastly interconnected global network of functionally associated PTM types in eukaryotes.
Central to the network of functionally associated PTM types appear phosphorylation, acetylation, ubiquitination and O‐linked glycosylation that control both temporal events and processes that govern protein localization.
There are >200 types of protein posttranslational modifications (PTMs) described in eukaryotes, each with unique proteome coverage and functions. We hypothesized that some genetic diseases may be ...caused by the removal of a specific type of PTMs by genomic variants and the consequent deregulation of particular functions. We collected >320,000 human PTMs representing 59 types and crossed them with >4M nonsynonymous DNA variants annotated with predicted pathogenicity and disease associations. We report >1.74M PTM-variant co-occurrences that an enrichment analysis distributed into 215 pairwise associations between 18 PTM types and 148 genetic diseases. Of them, 42% were not previously described. Removal of lysine acetylation exerts the most pronounced effect, and less studied PTM types such as S-glutathionylation or S-nitrosylation show relevance. Using pathogenicity predictions, we identified PTM sites that may produce particular diseases if prevented. Our results provide evidence of a substantial impact of PTM-specific removal on the pathogenesis of genetic diseases and phenotypes.
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•There is an enrichment of disease-associated nsSNVs preventing certain types of PTMs•We report 215 pairwise associations between 18 PTM types and 148 genetic diseases•The removal of lysine acetylation exerts the most pronounced effect•We report a set of PTM sites that may produce particular diseases if prevented
Omics, Proteomics, Systems Biology
Background
The European directive on basic safety standards (Council directive 2013/59 Euratom) mandates dosimetry-based treatment planning for radiopharmaceutical therapies. The directive comes into ...operation February 2018, and the aim of a report produced by the Internal Dosimetry Task Force of the European Association of Nuclear Medicine is to address this aspect of the directive. A summary of the report is presented.
Results
A brief review of five of the most common therapy procedures is included in the current text, focused on the potential to perform patient-specific dosimetry. In the full report, 11 different therapeutic procedures are included, allowing additional considerations of effectiveness, references to specific literature on quantitative imaging and dosimetry, and existing evidence for absorbed dose-effect correlations for each treatment. Individualized treatment planning with tracer diagnostics and verification of the absorbed doses delivered following therapy is found to be scientifically feasible for almost all procedures investigated, using quantitative imaging and/or external monitoring. Translation of this directive into clinical practice will have significant implications for resource requirements.
Conclusions
Molecular radiotherapy is undergoing a significant expansion, and the groundwork for dosimetry-based treatment planning is already in place. The mandated individualization is likely to improve the effectiveness of the treatments, although must be adequately resourced.
To provide a comprehensive overview of the molecular basis of autosomal dominant retinitis pigmentosa (adRP) in Spanish families. Thus, we established the molecular characterization rate, gene ...prevalence, and mutational spectrum in the largest European cohort reported to date.
A total of 258 unrelated Spanish families with a clinical diagnosis of RP and suspected autosomal dominant inheritance were included. Clinical diagnosis was based on complete ophthalmologic examination and family history. Retrospective and prospective analysis of Spanish adRP families was carried out using a combined strategy consisting of classic genetic techniques and next-generation sequencing (NGS) for single-nucleotide variants and copy number variation (CNV) screening.
Overall, 60% of our families were genetically solved. Interestingly, 3.1% of the cohort carried pathogenic CNVs. Disease-causing variants were found in an autosomal dominant gene in 55% of the families; however, X-linked and autosomal recessive forms were also identified in 3% and 2%, respectively. Four genes (RHO, PRPF31, RP1, and PRPH2) explained up to 62% of the solved families. Missense changes were most frequently found in adRP-associated genes; however, CNVs represented a relevant disease cause in PRPF31- and CRX-associated forms.
Implementation of NGS technologies in the adRP study clearly increased the diagnostic yield compared with classic approaches. Our study outcome expands the spectrum of disease-causing variants, provides accurate data on mutation gene prevalence, and highlights the implication of CNVs as important contributors to adRP etiology.
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