Impact of disposable syringes type choice on myocardial perfusion imaging procedures with [99mTc]Tc-tetrofosmin.

BACKGROUND: Residual activity in dispensing syringes is a problem that has been sporadically reported with various radiopharmaceuticals. Studies with [99mTc]Tc-tetrofosmin are non-consistent so far. The aim was to quantify the residual activity of [99mTc]Tc-tetrofosmin in different syringes in a clinical setting and to assess its impact on the clinical imaging procedure. METHODS: The residual activity of [99mTc]Tc-tetrofosmin was measured in 3 types of syringes: 3-part lubricated and non-lubricated syringes and 2-part syringe (n ≥ 30 for each syringe). The residual activity was located and quantified using a CzT SPECT camera and radio-counting then was correlated with different clinical parameters and processed by multiple linear regression analysis. RESULTS: Residual activity was different in all syringe types but lubricated syringes showed significantly higher levels with a mean ± SD of 26.12 ± 10.21% (P < .001). For these syringes, the residual activity was mainly located on the lubricated body. They also have a positive and significant impact on the standardized counting duration of patients' acquisitions. CONCLUSION: Lubricated syringes with high residual activity should be avoided as they increase the risk of prolonging patient acquisition time and potentially increasing the risk of poor image quality.

Quantitative impact of the first COVID-19 lockdown on nuclear medicine in France: the CORALINE study.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic reshaped the usual risk: benefit equilibrium that became a trade-off between the infection exposure risk for the patient (and for staff) and the risk associated with delaying or cancelling the nuclear medicine examination. This study aimed at quantifying the impact of the first COVID-19 lockdown in France on nuclear medicine examination volume together with volume of examination cancellation and non-attendance. METHODS: We retrospectively assessed the volume of planned examinations from 1 month before to 1 month after the first lockdown in French high-volume nuclear medicine departments (NMD) sharing the same information management system including both university hospitals, UH (n = 7), and cancer centres, CC (n = 2). RESULTS: The study enrolled 31,628 consecutive patients referred for a nuclear medicine examination performed or not (NMEP or NMEnP). The total volume of NMEP significantly dropped by 43.4% between the 4 weeks before and after the starting of the lockdown. The comparison of the percentage of NMEP and NMEnP between UH and CC is significantly different (p < 0.001). The percentage of NMEP during the study was 67.9% in UH vs 84.7% in CC. Percentages of NMEnP in UH and CC were due respectively to cancellation by the patient (14.9 vs 7.4%), cancellation by the NMD (9.5 vs 3.4%), cancellation by the referring physician (5.1 vs 4.4%) and non-attender patients (2.7 vs 0.2%). CONCLUSION: The study underlines the public health issue caused by COVID-19 above the pandemic itself and should be useful in preparing for potential resource utilisation and staffing requirements.

Advances in Radiopharmaceutical Sciences for Vascular Inflammation Imaging: Focus on Clinical Applications.

Biomedical imaging technologies offer identification of several anatomic and molecular features of disease pathogenesis. Molecular imaging techniques to assess cellular processes in vivo have been useful in advancing our understanding of several vascular inflammatory diseases. For the non-invasive molecular imaging of vascular inflammation, nuclear medicine constitutes one of the best imaging modalities, thanks to its high sensitivity for the detection of probes in tissues. 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) is currently the most widely used radiopharmaceutical for molecular imaging of vascular inflammatory diseases such as atherosclerosis and large-vessel vasculitis. The combination of [18F]FDG and positron emission tomography (PET) imaging has become a powerful tool to identify and monitor non-invasively inflammatory activities over time but suffers from several limitations including a lack of specificity and avid background in different localizations. The use of novel radiotracers may help to better understand the underlying pathophysiological processes and overcome some limitations of [18F]FDG PET for the imaging of vascular inflammation. This review examines how [18F]FDG PET has given us deeper insight into the role of inflammation in different vascular pathologies progression and discusses perspectives for alternative radiopharmaceuticals that could provide a more specific and simple identification of pathologies where vascular inflammation is implicated. Use of these novel PET tracers could lead to a better understanding of underlying disease mechanisms and help inform the identification and stratification of patients for newly emerging immune-modulatory therapies. Future research is needed to realize the true clinical translational value of PET imaging in vascular inflammatory diseases.

Nuclear Imaging: Focus on Vascular Probes

Noninvasive imaging technologies offer to identify several anatomic and molecular features of high-risk plaques. For the noninvasive molecular imaging of atherosclerotic plaques, nuclear medicine constitutes one of the best imaging modalities, thanks to its high sensitivity for the detection of probes in tissues. 18F-fluorodeoxyglucose (FDG) is currently the most widely used radiopharmaceutical for molecular imaging of atherosclerotic plaques with positron emission tomography. The intensity of FDG uptake in the vascular wall correlates closely with the degree of macrophage infiltration in atherosclerotic plaques. FDG positron emission tomographic imaging has become a powerful tool to identify and monitor noninvasively inflammatory activities in atherosclerotic plaques over time. This review examines how FDG positron emission tomographic imaging has given us deeper insight into the role of inflammation in atherosclerotic plaque progression and discusses perspectives for alternative radiopharmaceuticals to FDG that could provide a more specific and simple identification of high-risk lesions and help improve risk stratification of atherosclerotic patients. Visual Overview- An online visual overview is available for this article.

Inflammation imaging to define vulnerable plaque or vulnerable patient.

The role of nuclear imaging in the characterization of high-risk atherosclerotic plaque is increasing thanks to its high sensitivity to detect radiopharmaceuticals signal in tissues. Currently, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is the most studied and widely used radiopharmaceutical for the molecular imaging of atherosclerotic plaques with positron emission tomography (PET). [18F]FDG PET is a valuable tool to non-invasively detect, monitor and quantify inflammatory processes occurring in atherosclerotic plaques. The aim of this review is to gather insights provided by [18F]FDG PET to better understand the role of inflammation in the definitions of the vulnerable plaque and the vulnerable patient. Alternatives radiopharmaceuticals targeting inflammation and other potential high-risk plaque related processed are also discussed.

Nanostructured lipid carriers accumulate in atherosclerotic plaques of ApoE-/- mice.

Nanostructured lipid carriers (NLC) might represent an interesting approach for the identification and targeting of rupture-prone atherosclerotic plaques. In this study, we evaluated the biodistribution, targeting ability and safety of 64Cu-fonctionalized NLC in atherosclerotic mice. 64Cu-chelating-NLC (51.8±3.1 nm diameter) with low dispersity index (0.066±0.016) were produced by high pressure homogenization at tens-of-grams scale. 24 h after injection of 64Cu-chelated particles in ApoE-/- mice, focal regions of the aorta showed accumulation of particles on autoradiography that colocalized with Oil Red O lipid mapping. Signal intensity was significantly greater in aortas isolated from ApoE-/- mice compared to wild type (WT) control (8.95 [7.58, 10.16]×108 vs 4.59 [3.11, 5.03]×108 QL/mm2, P < 0.05). Moreover, NLC seemed safe in relevant biocompatibility studies. NLC could constitute an interesting platform with high clinical translation potential for targeted delivery and imaging purposes in atherosclerosis.

Imaging inflammation in atherosclerotic plaques: Just make it easy!

The presence of inflammatory cells is a hallmark of unstable atherosclerotic plaques. Several imaging approaches have been developed for the noninvasive detection of inflammatory activities in atherosclerotic plaques. Positron emission tomography (PET) imaging with the injection of 18F-fluorodeoxyglucose (FDG) is currently the most widely used imaging technique to evaluate the density of activated macrophages in atherosclerotic plaques. Nevertheless, FDG-PET imaging has logistical and technical constraints that represent an important obstacle to the wider use of this approach for the evaluation of patients with atherosclerosis. In a similar way as in the oncological field, the balance between the benefits and costs of new drugs need to be improved in patients with cardiovascular diseases. PET imaging of plaque inflammation might represent a very useful tool to identify patients who could benefit the most from anti-inflammatory treatments and to exclude patients with other causes of inflammation who are the most likely to develop severe side effects under these drugs. The availability of radiotracers targeting more specifically inflammation in atherosclerotic plaques would greatly facilitate the logistic organization of this imaging and help to expand the use of PET for the evaluation of atherosclerotic patients.

Cardiac denervation evidenced by MIBG occurs earlier than amyloid deposits detection by diphosphonate scintigraphy in TTR mutation carriers.

PURPOSE: Cardiac involvement in familial transthyretin (TTR) amyloidosis is of major prognostic value, and the development of early-diagnostic tools that could trigger the use of new disease-modifying treatments is crucial. The aim of our study was to compare the respective contributions of 99mTc-diphosphonate scintigraphy (DPD, detecting amyloid deposits) and 123I-MIBG (MIBG, assessing cardiac sympathetic denervation) in patients with genetically proven TTR mutation referred for the assessment of cardiac involvement. METHODS: We prospectively studied 75 consecutive patients (classified as symptomatic or asymptomatic carriers), using clinical evaluation, biomarkers (troponin and BNP), echocardiography, and nuclear imaging. Patients were classified as having normal heart-to-mediastinum (HMR) MIBG uptake ratio 4 h after injection (defined by HM4 ≥ 1.85) or abnormal HM4 < 1.85, and positive DPD uptake (grade ≥ 1 of Perugini classification) or negative DPD uptake. RESULTS: Among 75 patients, 49 (65%) presented with scintigraphic sympathetic cardiac denervation and 29 (39%) with myocardial diphosphonate uptake. When MIBG was normal, DPD was negative except for two patients. Age was an independent predictor of abnormal scintigraphic result of both MIBG and DPD (HR 1.08 and 1.15 respectively), whereas echocardiographic-derived indicators of increased left ventricular filling pressure (E/e' ratio) was an independent predictor of abnormal MIBG (HR 1.33) and global longitudinal strain of positive DPD (HR 1.45). In asymptomatic patients (n = 31), MIBG was abnormal in 48% (n = 15) among whom 50% had a normal DPD; all those with a normal MIBG (n = 16) had a normal DPD. CONCLUSIONS: In TTR mutation carriers, cardiac sympathetic denervation evidenced by decreased MIBG uptake is detected earlier than amyloid burden evidenced by DPD. These results raise the possibility of a diagnostic role for MIBG scintigraphy at an early stage of cardiac involvement in TTR-mutated carriers, in addition to its well-established prognostic value.

18F-FDG-PET/CT Imaging to Diagnose Septic Emboli and Mycotic Aneurysms in Patients with Endocarditis and Cardiac Device Infections.

PURPOSE OF REVIEW: This review analyzes recent studies evaluating the diagnostic value of 18F-FDG-PET/CT for the detection of peripheral emboli and secondary infectious foci in patients with infective endocarditis and cardiac device infections. RECENT FINDINGS: Detection of extracardiac septic localizations in patients with infective endocarditis and cardiac device infections is crucial, as it may impact the diagnosis, prognosis, and therapeutic management. Recent literature substantiated the clinical usefulness of 18F-FDG-PET/CT in this setting. 18F-FDG-PET/CT has proven its high diagnostic value for the detection of peripheral emboli in patients with infective endocarditis and cardiac device infections, substantially affecting patients' outcome and treatment. A multimodal approach, combining the high sensitivity of 18F-FDG-PET/CT with morphological imaging seems promising.

Container-content interactions with radiopharmaceuticals: Seeing is believing.

This perspective article addresses the critical issue of container-content interactions in the administration of intravenous medications, with a focus on radiopharmaceuticals used in nuclear medicine. Medication administration errors pose a significant challenge to patient safety. The "five rights" framework-ensuring the right patient, drug, time, dose, and route-serves as a cornerstone for safe drug administration. In the context of radiopharmaceuticals, notable for their use in nuclear medicine, adherence to these principles is paramount due to their unique properties and role in diagnostic and therapeutic procedures. The article explores the impact of container materials, particularly in syringes, on radiopharmaceutical stability and administration accuracy. It delves into the complexities of sorption phenomena, highlighting studies demonstrating its occurrence and potential consequences, including variations in administered doses and compromised diagnostic or therapeutic outcomes. Noteworthy factors influencing sorption include the type of radiopharmaceutical, container composition, molecular properties, and dilution. Findings revealing residual activity in syringes and identifying specific components, such as lubricants, silicon gaskets, and plungers, contributing to adsorption are presented. Migration of metal contaminants from container to content is discussed, emphasizing the potential impact on radiochemical yield and stability. There is a need for comprehensive studies to characterize drug-container interactions and poses crucial questions about the true benefit patients derive from prescribed activities. It challenges current practices, suggesting a need for tailored activity levels, container validation protocols, and rigorous testing of hospital preparations. Ultimately, this perspective paper calls for a deeper understanding of these interactions, urging regulatory consideration and standardization to ensure optimal drug administration and patient outcomes.

Optimised quality control method for determination of the radiochemical purity of [99mTc]Tc-mebrofenin and [99mTc]Tc-etifenin in a clinical context.

OBJECTIVES: In the context of a supply disruption of mebrofenin (Cholediam)-based kits for radiolabelling with technetium-99m [99mTc], the medicine agencies allowed the importation of a back-up radiopharmaceutical diagnostic agent, etifenin (Techida), to ensure continuous management of patients with hepatobiliary disorders in nuclear medicine departments. There are still issues regarding the measurement of radiochemical purity (RCP) with these kits based on the European Pharmacopoeia and the Summary of Product Characteristics (SPC). This study aims to identify and to optimise, in a clinical context, the most suitable thin layer chromatography (TLC) method for the determination of the RCP in terms of speed of response and reliability for [99mTc]Tc-mebrofenin and [99mTc]Tc-etifenin. METHODS: [99mTc]Tc-etifenin (n=4) and [99mTc]Tc-mebrofenin (n=5) were individually controlled using six different TLC methods and one high-performance liquid chromatography (HPLC) method for impurity identification ([99mTc](TcO2)n and Na[99mTc]TcO4), RCP (%) and duration of analysis (min). Two TLC methods were selected according to the recommendations of the Pharmacopoeia and SPC, two others were exactly the same but with a heating step, and the other two corresponded to a mix between the methods of the SPC and the Pharmacopoeia that were chosen to optimise RCP determination parameters. RESULTS: Radio-HPLC analysis allowed effective separation of [99mTc]Tc-etifenin and [99mTc]Tc-mebrofenin with a retention time of 8.05±0.02 min and 8.94±0.07 min, respectively, from Na[99mTc]TcO4 (retention time 2.76±0.03 min). HPLC showed an absence of Na[99mTc]TcO4 for [99mTc]Tc-mebrofenin and 0.2% for [99mTc]Tc-etifenin. Among the TLC methods, we identified the most suitable method which ensures the most compliant RCP (98.3±0.9%) in a time of 31.5±1.1 min. Also, it allowed a time saving of 15 min compared with the methods proposed by the Pharmacopoeia and the SPCs. CONCLUSION: We propose a TLC method that accelerates quality control by an average of 15 min while guaranteeing a reliable RCP.

Transferability of a two-strip method for the quality control of technetium-99m mercaptoacetyltriglycine ([99mTc]Tc-MAG3).

OBJECTIVES: Technetium-99m mercapto-acetyl-triglycine ([99mTc]Tc-MAG3) is a radiopharmaceutical diagnostic agent used in nuclear medicine intended for the exploration of nephrological and urological disorders. Patient safety and reliability of this imaging procedure especially depend on the radiochemical purity (RCP) of the [99mTc]Tc-MAG3 preparation. Recently, the Summary of Product Characteristics (SPC) of NephroMAG, a kit dedicated to [99mTc]Tc-MAG3 preparation, proposed a two-strip thin layer chromatography (TLC) based quality control (QC) method. Also, Straub et al recently proposed another TLC based QC method. We sought to evaluate the transferability of these QC methods in our hospital radiopharmacy and compared them to our currently employed TLC method and radio-HPLC (high-pressure liquid chromatography) to select the most appropriate in the context of hospital radiopharmacy. METHODS: Ten consecutive [99mTc]Tc-MAG3 preparations were controlled using: HPLC combined with a radiodetector (radio-HPLC), a single strip TLC method (method 1) in current use in our centre, a two-strip TLC method described in the SPC (method SPC) and a two-strip TLC method (method 2) described by Straub et al. Quantitative results for the four tested QC methods were measured and compared in terms of RCP (%), sodium pertechnetate ([99mTc]TcO4 -) (%) and duration of analysis (min). RESULTS: RCP was significantly different between method SPC and radio-HPLC (p<0.001) and method 2 (p<0.001). Also, the percentage of [99mTc]TcO4 - was statistically different between the radio-HPLC and the method SPC (p<0.001), but not with the method 1 and method 2 group (p>0.05). The duration of analysis (min) was significantly different between the four QC procedures (p<0.001) with method 2 and method SPC being the quickest. CONCLUSIONS: Our study showed it is possible to transfer and select a quick and reliable QC method for the preparation of NephroMAG kits in our centre. We therefore advise the widespread use of the method from Straub et al in hospital radiopharmacies.

Safety and Therapeutic Optimization of Lutetium-177 Based Radiopharmaceuticals.

Peptide receptor radionuclide therapy (PRRT) using Lutetium-177 (177Lu) based radiopharmaceuticals has emerged as a therapeutic area in the field of nuclear medicine and oncology, allowing for personalized medicine. Since the first market authorization in 2018 of [¹77Lu]Lu-DOTATATE (Lutathera®) targeting somatostatin receptor type 2 in the treatment of gastroenteropancreatic neuroendocrine tumors, intensive research has led to transfer innovative 177Lu containing pharmaceuticals to the clinic. Recently, a second market authorization in the field was obtained for [¹77Lu]Lu-PSMA-617 (Pluvicto®) in the treatment of prostate cancer. The efficacy of 177Lu radiopharmaceuticals are now quite well-reported and data on the safety and management of patients are needed. This review will focus on several clinically tested and reported tailored approaches to enhance the risk-benefit trade-off of radioligand therapy. The aim is to help clinicians and nuclear medicine staff set up safe and optimized procedures using the approved 177Lu based radiopharmaceuticals.

Management and evaluation of sodium [131I] iodide contamination after oral administration.

Radioiodine therapy using oral administration of Iodine-131 (I) is a widespread employed strategy for the treatment of hyperthyroidism and thyroid cancer. Such a therapy requires well-trained staff, equipment and procedures regarding radiation safety. The aims of this work are to report an incidental experience of radioprotection with a 370 MBq sodium [I] iodide capsule, which arose following vomiting one minute after the oral administration in a nuclear medicine department and assessment of capsule leakage in a stomach like environment by in vitro experiment. Measurements of the radiation dose rate at the different steps of the decontamination procedure were performed and management of the situation described. Dose rate in vomit was 113 µSv/h [directional dose equivalent H'(0.07)] after capsule withdrawal and was decreased by 10 times after the first decontamination attempt. To evaluate the I release following administration to the patient, an in vitro experiment was designed to recap capsules degradation in a stomach like environment including acidic solution (pH 1) and temperature at 35-37°c. A significant release of I (<6%) was observed in the first 2 min of the in vitro experiment. Sodium [I] iodide capsules disruption occurred at 150 s for capsule 1 and 133 s for capsule 2. Incidental contamination with I in the clinics is of important concern in nuclear medicine and precautions that allow optimization and pertinent management of the situation should be known by the nuclear medicine and radioprotection community.

Early Detection of Localized Immunity in Experimental Autoimmune Myocarditis Using [99mTc]Fucoidan SPECT.

PURPOSE: The aim of the study was to evaluate the ability of technetium-99m-fucoidan ([99mTc]fucoidan), a molecular imaging agent specific for selectins, in the assessment of early localized immunity in a rat model of experimental autoimmune myocarditis (EAM). PROCEDURES: EAM was induced in Lewis rats and troponin T; brain natriuretic peptide (BNP) and anti-myosin antibodies were measured in plasma. Separately, [99mTc]fucoidan single-photon emission computed tomography (SPECT)/x-ray computed tomography (CT) was performed in the very early phase of myocarditis at 10, 15, and 21 days after immunization. Then, hearts were collected and used for autoradiography, well counting, histology, and flow cytometry analysis. RESULTS: The EAM acute phase is characterized by extensive myocardial necrosis, release of troponin and BNP, and pericardial effusion. [99mTc]Fucoidan uptake was significantly increased in EAM compared with controls starting from D15. There was a close relationship between uptake of the tracer and myocardial content in CD45+, CD8+, CD11b+, and CD31+ cells. CONCLUSIONS: [99mTc]Fucoidan SPECT/CT accurately diagnosed the autoimmune attack in the early steps of EAM and could be used to monitor disease evolution and therapy efficiency.