Fibroblast Activation Protein Inhibitor PET/CT in Gastric Cancer.

Like other major cancers, gastric cancer expresses fibroblast activation protein (FAP) in cancer-associated fibroblasts. Many recent studies have reported the utility and superiority of FAP inhibitor (FAPI)-PET over [18F]fluorodeoxyglucose (FDG)-PET in gastric cancers, from initial staging to recurrence detection. FAPI-PET shows higher accumulation in primary sites and metastatic lesions than does FDG-PET, especially for the detection of peritoneal carcinomatosis. In the case of gastric signet ring cell carcinoma, FAPI-PET showed excellent performance, as uptake is usually weak on FDG-PET in this cohort.

Common Shortcomings in Study on Radiopharmaceutical Design Research: A Case Study of 99mTc-Labelled Methotrexate.

The aim of the work carried out was to draw attention to shortcomings that often appear at the stage of designing new radiopharmaceuticals. Based on a case study of 99mTc-labelled methotrexate, this article describes frequent mistakes or misconceptions present not only in the referenced studies, but also in numerous radiopharmaceutical studies. The recommendations provided in this article highlight fundamental aspects of the credibility of radiopharmaceutical scientific research leading to the reliable results.

Nuclear Medicine Imaging Procedures in Oncology.

Nuclear medicine radionuclide imaging is a quantitative imaging modality based on radioisotope-labeled tracers which emit radiation in the form of photons used for image reconstruction. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are the two noninvasive tomographic three-dimensional radionuclide imaging procedures for both clinical and preclinical settings. In this review on nuclear medicine imaging procedures in oncology, a variety of standard SPECT and PET tracers including radioiodine, 18Fluorine fluorodeoxyglucose (18F-FDG), and 68Gallium-labeled small proteins like Prostate Specific Membrane Antigen (PSMA) or somatostatin analogues and their application as targeted molecular imaging probes for improved tumor diagnosis and tumor phenotype characterization are described. Absolute and semiquantitative approaches for calculation of tracer uptake in tumors during the course of disease and during treatment allow further insight into tumor biology, and the combination of SPECT and PET with anatomical imaging procedures like computed tomography (CT) or magnetic resonance imaging (MRI) by hybrid SPECT/CT, PET/CT, and PET/MRI scanners provides both anatomical information and tumor functional characterization within one imaging session. With the recent establishment of novel molecular radiolabeled probes for specific tumor diagnosis, prognosis, and treatment monitoring, nuclear medicine has been able to establish itself as a distinct imaging modality with increased sensitivity and specificity.

IAEA Activities on 67Cu, 186Re, 47Sc Theranostic Radionuclides and Radiopharmaceuticals.

Despite interesting properties, the use of 67Cu, 186Re and 47Sc theranostic radionuclides in preclinical studies and clinical trials is curtailed by their limited availability due to a lack of widely established production methods. An IAEA Coordinated Research Project (CRP) was initiated to identify important technical issues related to the production and quality control of these emerging radionuclides and related radiopharmaceuticals, based on the request from IAEA Member States. The international team worked on targetry, separation, quality control and radiopharmaceutical aspects of the radionuclides obtained from research reactors and cyclotrons leading to preparation of a standard recommendations for all Member States. The CRP was initiated in 2016 with fourteen participants from thirteen Member States from four continents. Extraordinary results on the production, quality control and preclinical evaluation of selected radionuclides were reported in this project that was finalized in 2020. The outcomes, outputs and results of this project achieved by participating Member States are described in this minireview.

Hospital Radiopharmacy in Argentina during the COVID-19 pandemic. Criteria and rationale for the organization of work. / Radiofarmacia Hospitalaria en Argentina durante la pandemia de COVID-19. Criterios y fundamentos para la organización del trabajo.

This publication presents criteria and bases for the work organization in the safe practice of Hospital Radiopharmacy, in order to minimize the risk of viral transmission during the COVID-19 pandemic, in a reference facility of the National Energy Commission Atomic of Argentina, while continuing to perform essential services for the health system. For this purpose, documents from the National Energy Commission Atomic, IAEA, WHO and other scientific publications were consulted as reference. These recommendations are under constant review and are permanently updated. Within this framework, the present model of work organization for this essential activity is proposed, including general and specific recommendations and its epidemiological and immunological basis.

Biosynthetic new composite material containing CuO nanoparticles produced by Aspergillus terreus for 47Sc separation of cancer theranostics application from irradiated Ca target.

Copper oxide nanoparticles (CuO NPs) are needed in various fields, especially in the biomedical field. CuO NPs was obtained from Aspergillus terreus filtrate. CuO NPs structure was confirmed by UV-Vis spectrophotometry, as well as Fourier transform infrared (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). XRD offers the nanoparticles purity of CuO biosynthesis. CuO NPs are spherical when examined with TEM. The average size of CuO NPs from TEM was 15.75 ± 3.95 nm. New composite of P (AA-AN)-NPs CuO was synthesized by biotechnology and the induced γ-radiation. The distribution coefficient value (Kd) of 47Sc(III) as well as 47Ca(II) ions for the synthetic new composite was determined by batch technique. Radiochemical separation of 47Sc(III) from irradiated calcium target was studied using chromatographic column packed with the new composite material. The recovery yield of 78 ± 1.2% for 47Sc(III) was obtained using 1 M HCl. The quality control tests (chemical, radionuclide and radiochemical purities) of the eluted 47Sc confirmed that it's adequate for nuclear medicine applications.

ARRONAX Cyclotron: Setting up of In-House Hospital Radiopharmacy.

Whilst radiopharmaceuticals have an important role to play in both imaging and treatment of patients, most notably cancer patients, nuclear medicine and radiopharmacy are currently facing challenges to create innovative new drugs. Traditional radiopharmaceutical manufacture can be considered as either a routine hospital production or a large-scale industrial production. The gap between these two practices has meant that there is an inability to supply innovative radiopharmaceuticals for use at the local level for mono- or multicentric clinical trials with satisfactory quality and safety specifications. This article highlights the regulatory requirements in aseptic pharmaceutical processing and in nuclear medicine to be able to locally produce radiopharmaceuticals. We validate the proof-of-concept for an "in-house" hospital-based radiopharmacy including an on-site cyclotron, that can fulfill the conflicting requirements between radiation safety and aseptic processing. The ARRONAX in-house radiopharmacy is currently able to provide sterile and pyrogenic-free injectable radiopharmaceutical compounds for both industrial and institutional clinical trials.

Comparison of 5 Different PET Radiopharmaceuticals for the Detection of Recurrent Medullary Thyroid Carcinoma: A Network Meta-analysis.

PURPOSE: The aim of this study is to investigate and compare the performance of different PET radiopharmaceuticals for the detection of recurrent medullary thyroid carcinoma (MTC) by performing a network meta-analysis (NMA) using direct comparison studies with 2 or more PET radiopharmaceuticals. METHODS: PubMed and EMBASE were searched for the studies evaluating the performance of PET or PET/CT for the detection of recurrent MTC. The NMA was performed for different PET radiopharmaceuticals in both patient- and lesion-based analyses and with a threshold of serum calcitonin or carcinoembryonic antigen (CEA) levels and calcitonin doubling time. The consistency was evaluated by examining the agreement between direct and indirect treatment effects, and publication bias was assessed by funnel plot asymmetry tests. The surface under the cumulative ranking curve values were obtained to calculate the probability of each PET modality being the most effective diagnostic method. RESULTS: A total of 306 patients from 14 direct comparison studies using 5 different PET radiopharmaceuticals (F-FDG, F-DOPA, Ga-somatostatin analogs, 3-O-methyl-6-[F]fluoro-DOPA, and C-methionine) for the detection of recurrent MTC was included. The detection rate of F-DOPA PET was significantly higher than that of FDG PET in both patient- and lesion-based analyses (patient-based analysis: odds ratio, 2.44; 95% confidence interval, 1.4-4.31; lesion-based analysis: odds ratio, 5.74; 95% confidence interval, 1.65-23.4). Among all PET radiopharmaceuticals, F-DOPA showed the highest surface under the cumulative ranking curve value in both patient- and lesion-based analyses regardless of serum calcitonin or CEA levels and calcitonin doubling time. CONCLUSIONS: The results from this NMA indicate that F-DOPA PET clearly showed a best performance for the detection of recurrent MTC in both patient- and lesion-based analyses regardless of serum calcitonin or CEA levels and calcitonin doubling time.

Recomendaciones para la nomenclatura de compuestos radiomarcados / Recommendations for the nomenclature of radiolabeled compounds

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The Production, Quality Control, and Characterization of ZED8, a CD8-Specific 89Zr-Labeled Immuno-PET Clinical Imaging Agent.

Immuno-PET is a molecular imaging technique utilizing positron emission tomography (PET) to measure the biodistribution of an antibody species labeled with a radioactive isotope. When applied as a clinical imaging technique, an immuno-PET imaging agent must be manufactured with quality standards appropriate for regulatory approval. This paper describes methods relevant to the chemistry, manufacturing, and controls component of an immuno-PET regulatory filing, such as an investigational new drug application. Namely, the production, quality control, and characterization of the immuno-PET clinical imaging agent, ZED8, an 89Zr-labeled CD8-specific monovalent antibody as well as its desferrioxamine-conjugated precursor, CED8, is described and evaluated. PET imaging data in a human CD8-expressing tumor murine model is presented as a proof of concept that the imaging agent exhibits target specificity and comparable biodistribution across a range of desferrioxamine conjugate loads.

Facile fully automated radiosynthesis and quality control of O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) for human brain tumor imaging.

O-(2-[18F]Fluoroethyl)-l-tyrosine ([18F]FET) has become one of the most successful amino acid tracers for human brain tumor imaging with positron emission tomography (PET). Facile fully automated radiosynthesis and quality control (QC) of [18F]FET using our home-built automated multi-purpose 18F-radiosynthesis module are described. [18F]FET was produced in 75-80 min overall synthesis time with 20-25% radiochemical yield decay corrected to end of bombardment (EOB), based on H[18F]F. The radiochemical and enantiomeric purities were >99%, and the molar activity (Am) was 189-411 GBq/µmol at EOB. The [18F]FET dose meets all QC criteria for clinical use, and is suitable for clinical PET study of brain tumor.

European Association of Nuclear Medicine Practice Guideline/Society of Nuclear Medicine and Molecular Imaging Procedure Standard 2019 for radionuclide imaging of phaeochromocytoma and paraganglioma.

PURPOSE: Diverse radionuclide imaging techniques are available for the diagnosis, staging, and follow-up of phaeochromocytoma and paraganglioma (PPGL). Beyond their ability to detect and localise the disease, these imaging approaches variably characterise these tumours at the cellular and molecular levels and can guide therapy. Here we present updated guidelines jointly approved by the EANM and SNMMI for assisting nuclear medicine practitioners in not only the selection and performance of currently available single-photon emission computed tomography and positron emission tomography procedures, but also the interpretation and reporting of the results. METHODS: Guidelines from related fields and relevant literature have been considered in consultation with leading experts involved in the management of PPGL. The provided information should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals. CONCLUSION: Since the European Association of Nuclear Medicine 2012 guidelines, the excellent results obtained with gallium-68 (68Ga)-labelled somatostatin analogues (SSAs) in recent years have simplified the imaging approach for PPGL patients that can also be used for selecting patients for peptide receptor radionuclide therapy as a potential alternative or complement to the traditional theranostic approach with iodine-123 (123I)/iodine-131 (131I)-labelled meta-iodobenzylguanidine. Genomic characterisation of subgroups with differing risk of lesion development and subsequent metastatic spread is refining the use of molecular imaging in the personalised approach to hereditary PPGL patients for detection, staging, and follow-up surveillance.

Clinical and dosimetric considerations for Y90: recommendations from an international multidisciplinary working group.

The TheraSphere Global Dosimetry Steering Committee was formed in 2017 by BTG International to review existing data and address gaps in knowledge related to dosimetry. This committee is comprised of health care providers with diverse areas of expertise and perspectives on radiation dosimetry. The goal of these recommendations is to optimize glass microspheres radiation therapy for hepatocellular carcinoma while accounting for variables including disease presentation, tumour vascularity, liver function, and curative/palliative intent. The recommendations aim to unify glass microsphere users behind standardized dosimetry methodology that is simple, reproducible and supported by clinical data, with the overarching goal of improving clinical outcomes and advancing the knowledge of dosimetry.

Autoradiography validation of novel tau PET tracer [F-18]-MK-6240 on human postmortem brain tissue.

[F-18]-MK-6240, a novel tau positron emission tomography (PET) tracer recently discovered for the in vivo detection of neurofibrillary tangles, has the potential to improve diagnostic accuracy in the detection of Alzheimer disease. We have examined regional and substrate-specific binding patterns as well as possible off-target binding of this tracer on human brain tissue to advance towards its validation. We applied [F-18]-MK-6240 phosphor screen and high resolution autoradiography to postmortem samples from patients with a definite pathological diagnosis of Alzheimer disease, frontotemporal lobar degeneration-tau (Pick's disease, progressive supranuclear palsy and corticobasal degeneration), chronic traumatic encephalopathy, frontotemporal lobar degeneration-Tar DNA-binding protein 43 (TDP-43), dementia with Lewy bodies, cerebral amyloid angiopathy and elderly controls free of pathologic changes of neurodegenerative disease. We also directly compared the binding properties of [F-18]-MK-6240 and [F-18]-AV-1451 in human tissue, and examined potential nonspecific binding of both tau tracers to monoamine oxidases (MAO) by using autoradiography in the presence of selective monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) inhibitors. Our data indicate that MK-6240 strongly binds to neurofibrillary tangles in Alzheimer disease but does not seem to bind to a significant extent to tau aggregates in non-Alzheimer tauopathies, suggesting that it may have a limited utility for the in vivo detection of these pathologies. There is no evidence of binding to lesions containing ß-amyloid, α-synuclein or TDP-43. In addition, we identified MK-6240 strong off-target binding to neuromelanin and melanin-containing cells, and some weaker binding to areas of hemorrhage. These binding patterns are nearly identical to those previously reported by our group and others for [F-18]-AV-1451. Of note, [F-18]-MK-6240 and [F-18]-AV-1451 autoradiographic binding signals were only weakly displaced by competing concentrations of selective MAO-B inhibitor deprenyl but not by MAO-A inhibitor clorgyline, suggesting that MAO enzymes do not appear to be a significant binding target of any of these two tracers. Together these novel findings provide relevant insights for the correct interpretation of in vivo [F-18]-MK-6240 PET imaging.

Development of a remote purification apparatus with disposable evaporator for the routine production of high-quality 64Cu for clinical use.

We developed a new apparatus for the routine production of 64Cu in clinical use. The apparatus has many disposable parts that stabilize the product quality (such that there is a low deviation of the concentrations of impurity metals in the product) and reduce the work load of preparation for routine production. We also developed a new evaporator using near-infrared heaters for disposable use. We conducted a production test using the new apparatus and evaluated product quality. The product yield was 6.3 ±â€¯0.32 GBq (end of bombardment) (N = 4), the product quality in terms of the concentrations of impurity metals (Cu2+, Ni2+, Fe3+, Zn2+, Mn2+) was as good as that usually achieved, likely on the order of parts per billion, and the preparation time was reduced from 2 days to 1 day.

The potential radio-immunotherapeutic α-emitter 227Th - part II: Absolute γ-ray emission intensities from the excited levels of 223Ra.

At the time of publication, radiopharmaceuticals labelled with thorium-227 are in clinical trials in Europe for the treatment of various types of cancer. In part I of this two-part series the primary standardisation of an aqueous solution of 227Th was reported. In part II, the activity derived from the recommended absolute γ-ray emission intensities have been compared to that from the primary standardisation techniques. This comparison showed a negative bias of 4% in the determined activity per unit mass with an 11% spread in the activities determined for the eight most intense γ-ray emissions (Iγ > 1%) from the 227Th α decay. Using the standardised 227Th, measurements of the characteristic γ-ray emissions from the 223Ra excited states were made using a calibrated HPGe γ-ray spectrometer. This has enabled the absolute intensities of 70 γ ray emissions from the 227Th α-decay to be experimentally determined. A significant improvement over the precision of the recommended normalisation scaling factor has been made, with a value of 12.470 (35) % determined. Typically, the precision of the intensities has been improved by an order of magnitude or greater than current recommended values. The correlation matrices for pairs of the most intense γ-ray emission intensities are presented.