Search

Objectives: In the context of a supply disruption of mebrofenin (Cholediam)-based kits for radiolabelling with technetium-99m [ 99m Tc], 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 [ 99m Tc]Tc-mebrofenin and [ 99m Tc]Tc-etifenin., Methods: [ 99m Tc]Tc-etifenin (n=4) and [ 99m Tc]Tc-mebrofenin (n=5) were individually controlled using six different TLC methods and one high-performance liquid chromatography (HPLC) method for impurity identification ([ 99m Tc](TcO 2 ) n and Na[ 99m Tc]TcO 4 ), 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 [ 99m Tc]Tc-etifenin and [ 99m Tc]Tc-mebrofenin with a retention time of 8.05±0.02 min and 8.94±0.07 min, respectively, from Na[ 99m Tc]TcO 4 (retention time 2.76±0.03 min). HPLC showed an absence of Na[ 99m Tc]TcO 4 for [ 99m Tc]Tc-mebrofenin and 0.2% for [ 99m Tc]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., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Residual activity in dispensing syringes is a problem that has been sporadically reported with various radiopharmaceuticals. Studies with [ 99m Tc]Tc-tetrofosmin are non-consistent so far. The aim was to quantify the residual activity of [ 99m Tc]Tc-tetrofosmin in different syringes in a clinical setting and to assess its impact on the clinical imaging procedure., Methods: The residual activity of [ 99m Tc]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., (© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Objectives: Technetium-99m mercapto-acetyl-triglycine ([ 99m Tc]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 [ 99m Tc]Tc-MAG3 preparation. Recently, the Summary of Product Characteristics (SPC) of NephroMAG, a kit dedicated to [ 99m Tc]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 [ 99m Tc]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 ([ 99m Tc]TcO 4 - ) (%) 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 [ 99m Tc]TcO 4 - 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., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Peptide receptor radionuclide therapy (PRRT) using Lutetium-177 ( 177 Lu) 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 177 Lu 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 177 Lu 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 177 Lu based radiopharmaceuticals.

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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The medical management of patients, which involves securing the drug circuit, is a major public health objective. As part of quality management, a number of risk assessment and risk management tools in care units are validated and available. However, medication management in radiopharmacy departments represents a complex and specific process. The aim of the "Quality guidelines for radiopharmacy" working group of the French society of radiopharmacy (SoFRa) was to develop a risk-assessment tool that is a priori adapted to radiopharmacy activity., Methods: A qualitative risk matrix was developed, based on available analysis tools and current regulations concerning radiopharmacy practice. The tool was then programmed to obtain a summary and scoring for each risk category, as well as a quantitative analysis of the risks identified in radiopharmacy., Results: Our tool contains 262 issues. The qualitative study integrates the risks related to the circuit of radiopharmaceuticals, but also risks related to personnel. The quantitative study makes it possible to carry out an automated analysis of the actions to carry out in priority to improve the practices., Conclusions: This work led to the development of a self-assessment tool for the a priori analysis of risks that are adapted to the practice of radiopharmacy. It allows easy analysis of the entire circuit of radiopharmaceuticals from a single tool and meet the expectations of health authorities. This common and validated tool is available to the pharmaceutical community., (Copyright © 2021 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Background: Refining the risk of malignancy in patients presenting with thyroid nodules with indeterminate cytology (IC) is a critical challenge. We investigated the performances of 18 F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) to predict malignancy. Methods: Between May 2016 and March 2019, 107 patients presenting with a thyroid nodule ≥15 mm with IC and eligible for surgery were included in this prospective study. Head-and-neck PET/CT acquisitions were performed 20 and 60 minutes after injection of 1.5 MBq/kg of FCH. PET/CT acquisition was scored positive when maximal standardized uptake value in the IC nodule was higher than in the thyroid background. Pathology was the gold standard for diagnosis. Results: At pathology, 19 (18%) nodules were malignant, 87 were benign, and one was a noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Sensitivity, specificity, accuracy, positive-predictive value (PPV), and negative-predictive value (NPV) of FCH PET/CT in detecting cancer or NIFTP were 90%, 50%, 55%, 29%, and 96% at 20 minutes and 85%, 49%, 67%, 28%, and 94% at 60 minutes, respectively. Higher specificity (58% vs. 33%, p  = 0.01) was observed in nononcocytic ( n  = 72) than in oncocytic IC nodules ( n  = 35). The pre-PET/CT probability of cancer or NIFTP in Bethesda III-IV nodules was 11% and the post-PET/CT probability was 19% in PET-positives and 0% in PET-negatives. In retrospective analysis, 42% of surgeries would have been unnecessary after PET/CT and 81% before ( p  < 0.001), resulting in a hypothetical 48% reduction (95% confidence interval [32-64]). Conclusions: FCH PET/CT offers high NPV to reliably exclude cancer in PET-negative IC nodules, but suffers from low PPV, particularly in those with oncocytic cytology. ClinicalTrials.gov identifier: NCT02784223.

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.

The Radiopharmaceutical Health Products circuit or RHP (radiopharmaceutical drugs, radiopharmaceutical preparation and radioactive implantable medical devices) is a complex process that nowadays requires computerization. This circuit must be in accordance with both the legislation on medicinal products and the legislation on artificial radioelements. It is acknowledged that computerization of the circuit; possibly different within each organization, provides assistance to stakeholders: pharmaceutical analysis of prescription, pharmaceutical preparation and preparation of doses to be dispensed and waste management for example. The software also allows real-time monitoring of the activity and traceability of the various pharmaceutical processes. In addition, they are generally interfaced with equipment used routinely: dose calibrator, dose dispensing equipment. In the absence of any legislation for these software products, which are not considered either as medical devices or as software to assist prescription or dispensation, a working group, under the aegis of the Société Française de Radiopharmacie (SoFRa), has written a minimum set of specifications for these radiopharmaceutical software products. The analyses of the risk maps of different hospital structures allowed a global analysis and synthesis of the different processes, settings, interfaces and requirements for the proper use of these software. The specifications include the very specific requirements of radiopharmacy (notion of radioactive decay, complex preparations with chemical synthesis, traceability.) and will allow software publishers to propose tools adapted to our practice and the RHP circuit., (Copyright © 2019 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Nutritional care improves quality of life (QOL) in head and neck cancer patients treated with radiotherapy. The aim of our study was to determine whether intensive nutritional care (INC) would further improve QOL. In addition to a control group based on European and American guidelines, patients included in the INC group received six meetings with a dietitian. QOL was measured after radiotherapy using the EORTC QLQ-C30. We performed a meta-analysis to determine the best nutritional care. In the 87 patients, the QOL scores, weight, energy, and protein intakes were similar between the INC group (n = 43) and the control group (n = 44). The meta-analysis revealed no heterogeneity and significant differences in QOL (three studies) (p = 0.46) or weight changes after radiotherapy (four studies) (p = 0.06). The nutritional care specified in the European and American guidelines is composed of well-defined recommendations, and appears sufficient to maintain QOL without further intervention.

The TEKCIS technetium-99m (Tc) generator was designed to allow dry column shipment and automatized conception. A high Tc radioactive concentration is required in a subset of radiopharmacy procedures. Fractionated elution can be a useful tool to meet this requirement, especially when current elution is close to the generator expiration date. The aim of our study was to assess TEKCIS generator elution kinetics and to determine the optimal fractionated elution time to fit with procedures requiring the highest Tc radioactive concentration in clinical use. After duplicate elution at several predetermined elution times, the volume and activity of each eluate were measured. Two optimal time points were selected to perform fractionated elution and repeatability (n=34 and 33) assessed on TEKCIS generators calibrated at 6 or 8 GBq. The complete eluate volume (5 ml) was collected after 60 s of elution. A logarithmic equation was established between eluate volume (v, ml) from elapsed elution time (t, s): v=1.8335ln(t)-2.5965. Using the reciprocal equation, elution times required to obtain some commonly eluted volumes were calculated. Fractionated elutions during 15 and 20 s were selected and an average elution volume from 2.74 to 3.27 ml was collected, with an average elution yield of approximately 90 and 100%, respectively. Our work provides a simple and reliable methodology for the use of fractionated elution with the new TEKCIS generator.

Purpose: The aim of this study was to determine the potential diagnostic value of regional myocardial adrenergic (123)I-metaiodobenzylguanidine (MIBG) single photon emission computed tomography (SPECT) imaging to identify patients with Lewy body diseases (LBD+)., Methods: Sixty-four consecutive patients who underwent cardiac (123)I-MIBG SPECT to differentiate LBD+, including Parkinson's disease (PD) and dementia with Lewy bodies (DLB), from patients without LBD (LBD-) were retrospectively reviewed. A neurologist expert in memory disorders determined the final clinical diagnosis by using international clinical diagnostic criteria. Planar [heart to mediastinum ratio (HMR)] and (123)I-MIBG SPECT[(innervation defect score (IDS)] using the 17-segment left ventricular model (five-point scale) were obtained 4 h after the injection of (123)I-MIBG on a low-energy high-resolution (LEHR) collimator. Receiver-operating characteristic (ROC) analysis was performed to determine the optimal HMR and IDS cut-off values to discriminate LBD+ from LBD-., Results: Of the 64 patients, 45 (70 %) were diagnosed LBD+ (DLB, n = 27; PD, n = 18) and 19 were diagnosed LBD- (5 other dementias, 14 other parkinsonisms). The HMR and IDS of LBD+ were significantly different from those of LBD- (1.30 ± 0.21 vs 1.65 ± 0.26, p < 0.001; 39 ± 28 vs 8 ± 16, p = 0.001). The optimal HMR and IDS cut-off values to discriminate LBD+ (n = 45) from LBD- (n = 19) were 1.47 and 6/68, providing a sensitivity and specificity of 82.2 and 84.2% and 86.7 and 73.7%, respectively., Conclusion: Regional myocardial adrenergic (123)I-MIBG imaging SPECT has a potential diagnostic value to identify LBD+.

An efficient method to incorporate the fluorine-18 radionuclide in 2-nitropurine-based nucleosides was developed. The nucleophilic radiofluorination of the labeling precursor with [(18)F]KF under aminopolyether-mediated conditions (Kryptofix 2.2.2/K2CO3) followed by deprotection was straightforward and, after formulation, gave 2-[(18)F]fluoroadenosine, ready for injection with a radiochemical yield of 45 ± 5%, a radiochemical purity of >98%, and a specific radioactivity up to 148 GBq/μmol. A micropositron emission tomography imaging and biodistribution study on rodents was reported.

During the last decade, growing efforts have focused on human papillomavirus (HPV) detection using liquid hybridization, conventional PCR, and real-time PCR-based methods to increase the overall proportion of patients participating in cervical cancer screening procedures. We proposed a new general HPV DNA real-time PCR on the Mx4000 (Stratagene) and LightCycler (Roche Diagnostics) systems usable for both cervical scrape specimens and urine samples. A linear range was obtained from 5 DNA copies to 8 log(10) DNA copies/ml, and intra- and interassay variations were between 1.8 and 4%. Cervical carcinoma and HPV DNA screening was performed in 333 individual women referred for gynecological examination at the university hospitals of Angers and Brest and enrolled in the PapU study. Among cervical specimens (n = 333), 45% were positive for HPV DNA, with a mean viral load at 5.00 log/ml (+/- 1.73). Among urine samples (n = 177), 37% were positive with a significant 50-fold-lower mean viral load (3.77 +/- 1.32 log/ml; P < 0.0001). Kappa agreement for HPV DNA between cervical and urine specimens was excellent (93%). Thus, we developed a highly sensitive and quantitative general HPV DNA real-time PCR method that allows mass screening of patients with HPV infection. The ongoing longitudinal and prospective multicenter PapU study should give us the opportunity to validate this method adapted to HPV DNA screening in urine samples in a larger population.

The synthesis of 1,2-dioxolane derivatives in two different acetophenone series, as simplified models of natural coumarins is described. 2-Acetyl-3-acetoxy-4-(3-hydroperoxy-3-methylbut-1-enyl)phenyl acetate and 2-acetyl-5-acetoxy4-(3-hydroperoxy-3-methylbut-1-enyl) phenyl acetate synthons are used as precursors to these structures. In vitro antimalarial activity of the 1,2-dioxolane derivatives has been investigated.