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Background: The aim of this brief communication is to highlight the potential bacteriological risk linked to the processes control of radiopharmaceutical preparations made in a radiopharmacy laboratory. Survival rate of Pseudomonas aeruginosa (ATCC: 27853) or Staphylococcus aureus (ATCC: 25923) or Staphylococcus epidermidis (ATCC: 1228) in multidose technetium-99 m solution was studied. Results: Depending on the nature and level of contamination by pathogenic bacteria, the lethal effect of radioactivity is not systematically observed. We found that P. aeruginosa was indeed affected by radioactivity. However, this was not the case for S. epidermidis, as the quantity of bacteria found in both solutions (radioactive and non-radioactive) was rapidly reduced, probably due to a lack of nutrients. Finally, the example of S. aureus is an intermediate case where we observed that high radioactivity affected the bacteria, as did the absence of nutrients in the reaction medium. The results were discussed in the light of current practices on the sterility test method, which recommends waiting for radioactivity to decay before carrying out the sterility test. Conclusion: In terms of patient safety, the results run counter to current practice and the latest EANM recommendation of 2021 that radiopharmaceutical preparations should be decayed before sterility testing. [ABSTRACT FROM AUTHOR]

Background: Despite the development of positron emission tomography (PET), single photon emission computed tomography (SPECT) still accounts for around 80% of all examinations performed in nuclear medicine departments. The search for new radiotracers or chelating agents for Technetium-99m is therefore still ongoing. O-TRENSOX and O-TRENOX two synthetic siderophores would be good candidates for this purpose as they are hexadentate ligands based on the very versatile and efficient 8-hydroxyquinoline chelating subunit. First, the radiolabeling of O-TRENOX and O-TRENSOX with 99mTc was investigated. Different parameters such as the quantity of chelating agent, type of reducing agent, pH and temperature of the reaction mixture were adjusted in order to find the best radiolabeling conditions. Then an assessment of the partition coefficient by measuring the distribution of each radiosynthesized complex between octanol and phosphate-buffered saline was realized. The complex's charge was evaluated on three different celluloses (neutral, negatively charged P81 and positively charged DE81), and finally in vivo studies with biodistribution and SPECT imaging of [99mTc]Tc-O-TRENOX and [99mTc]Tc-O-TRENSOX were performed. Results: The radiolabeling studies showed a rapid and efficient complexation of 99mTc with both chelating agents. Using tin pyrophosphate as the reducing agent and a minimum of 100 nmol of ligand, we obtained the [99mTc]Tc-O-TRENOX complex with a radiochemical purity of more than 98% and the [99mTc]Tc-O-TRENSOX complex with one above 97% at room temperature within 5 min. [99mTc]Tc-O-TRENOX complex was lipophilic and neutral, leading to a hepatobiliary elimination in mice. On the contrary, the [99mTc]Tc-O-TRENSOX complex was found to be hydrophilic and negatively charged. This was confirmed by a predominantly renal elimination in mice. Conclusions: These encouraging results allow us to consider the O-TRENOX/99mTc and O-TRENSOX/99mTc complexes as serious candidates for SPECT imaging chelators. This study should be continued by conjugating these tris-oxine ligands to peptides or antibodies and comparing them with the other bifunctional agents used with Tc. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In Europe, where marine envenomations are usually not severe, some rare stings may require medical management; for example, weever fish stings, inducing numerous marine envenomations on the European coasts (these accidents lead to frequent consultations during the summer season in the French poison centers). The authors report the case of a 37-year-old man, without a previous clinical history, who was treated in an emergency unit for a weever fish sting on the scalp after a headlong fall in the sand. This observation was characterized by the unusual localization of the venom injection, and by the clinical feature of persistence of symptoms despite therapeutic treatment. [ABSTRACT FROM AUTHOR]

Automated compounding device (ACD) are increasingly used for parenteral nutrition (PN) bag production, and their acquisition must be sufficiently thought. The law requires the qualification of these ACD, but did not specify the tests to be performed. The quality by design (QbD) risk based approach allowed to define the quality target product profile in order to acquire the best ACD for each unit, and thanks a risk analysis permitted to define the critical quality attributes (CQA). These CQA will allowed to define tests performed during qualification. The ACD qualified was a 12 pump volumetric system. The CQA for PN bags consisted in sterile, precisely and accurately production with enough stability. During operational qualification volumetric accuracy test was performed, and during the performance qualification: flush volume, media fill, microbiological integrity of environment, sterility of control bag and production test were performed. At the end, all tests were conclusive (excepted for some results mostly due to analytical bias) and the ACD was considered to produce sterile bags in a control environment, precisely (relative standard deviation < 4%) and accurately (mean bias < 1% for weight and < 7% for other controls) with a sufficient stability. The QbD risk based approach allowed to acquire the best ACD for our need, and qualify relevant elements regarding the production process. [Display omitted] [ABSTRACT FROM AUTHOR]

Prostate Specific Membrane Antigen (PSMA) is a highly relevant target in nuclear medicine due to its overexpression in prostate cancer. The 68Ga/177Lu-PSMA-1 combination is a theranostic agent for the detection and treatment of tumors overexpressing the PSMA target. Specifically, 177Lu-PSMA-1 is used in the treatment of castration-resistant prostate cancer that is ineffective or intolerant to the latest generation of chemotherapy and/or hormone therapy. This radiopharmaceutical is manufactured in a radiopharmaceutical synthesizing unit and must pass a quality control where the radiochemical purity (RCP) is assessed prior to release of the batch. RCP evaluation is performed by high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). Since there is no monograph for 177Lu-PSMA-1 in the European Pharmacopoeia, we validate the analytical methods according to the EANM recommendations adapted from ICH Q2. Specificity, linearity, accuracy, precision, intermediate precision, limit of quantification (LOQ) and robustness were described for HPLC and TLC in this study. The results obtained demonstrated the robustness and reliability of the HPLC and TLC analytical methods for the evaluation of the RCP of 177Lu-PSMA-1. [ABSTRACT FROM AUTHOR]

Purpose: Coronary microvascular dysfunction (CMVD) plays a major role in the occurrence of cardiovascular events (CVE). We recently suggested the clinical potential of myocardial perfusion entropy (MPE) quantification from SPECT myocardial perfusion images (MPI) for the prognosis of CVE occurrence. We hypothesized that the quantification of MPE from SPECT MPI would allow the assessment of CMVD-related MPE variations in a preclinical model of type 2 diabetes (T2D) including treatment with the anti-diabetic incretin liraglutide (LIR). Methods: Optimal conditions for the preclinical quantification of MPE using 201Tl SPECT MPI were determined in rats with a T2D-like condition induced by a high-fat diet and streptozotocin injection (feasibility study, n = 43). Using such conditions, echocardiography and post-mortem LV capillary density evaluation were then used in order to assess the effect of LIR and the ability of MPE to assess CMVD (therapeutic study, n = 39). Results: The feasibility study identified dobutamine stress and acute NO synthase and cyclooxygenase inhibition as optimal conditions for the quantification of MPE, with significant increases in MPE being observed in T2D animals (P < 0.01 vs controls). In the therapeutic study, T2D rats were hyperglycemic (5.5 ± 0.5 vs 1.1 ± 0.3 g/L for controls, P < 0.001) and had a significantly lower left ventricular ejection fraction (LVEF) (65 ± 4% vs 74 ± 9%, P < 0.01) and LV capillary density (2400 ± 300 vs 2800 ± 600 mm−3, P < 0.05). LIR partially restored glycemia (3.9 ± 0.6 g/L, P < 0.05 vs controls and T2D), totally prevented LVEF impairment (72 ± 7%, P = NS vs CTL), with no significant effect on capillary density. MPE was significantly increased in T2D rats (7.6 ± 0.5 vs 7.1 ± 0.5, P < 0.05), with no significant improvement in T2D-LIR rats (7.4 ± 0.4, P = NS vs controls and T2D). Conclusion: MPE quantification allowed the preclinical noninvasive assessment of CMVD. Both MPE and capillary density quantification suggested that LIR did not improve T2D-induced CMVD. The relevance of MPE for CMVD assessment warrants further clinical investigation. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases, including fatal myocardial infarctions from atheromatous plaques, are the primary global mortality cause. Detecting stenotic atheromatous plaques is possible through coronary angiography, but vulnerable plaques with eccentric remodeling are undetectable with current diagnostic methods. Addressing this challenge, our group developed a radiopharmaceutical drug targeting vascular cell adhesion molecule 1 (VCAM-1), radiolabeled with technetium-99m. Given the absence of a monograph in the European Pharmacopoeia, and in order to draft the investigational medicinal product documentation, analytical methods had to be validated by high performance liquid chromatography (HPLC) and thin layer chromatography (TLC) to determine the radiochemical purity (RCP) of 99mTc-cAbVCAM1–5. This study therefore presents the results of the validation of analytical methods obtained in this context. The method validation followed the European Association of Nuclear Medicine (EANM) recommendations adapted from ICH Q2(R1), ensuring conformity with specificity, accuracy, repeatability and intermediate precision, linearity, robustness, quantification limit (LoQ), and range criteria. Regarding the results of specificity, both HPLC and TLC methods demonstrated excellent separation of 99mTc-cAbVCAM1–5 from impurities 99mTcO4-. Accuracy results indicated recovery percentages within the range of 99.52–101.40% for the HPLC and 99.51–101.97% for TLC, ensuring reliable measurements for each concentration of 99mTcO 4 -. Precision of the methods was validated by assessing repeatability and intermediate precision. Linearity was determined over the usual concentrations range and the correlation coefficient was greater than 0.99 for both methods. The limit of quantification was measured by diluting the 99mTcO 4 - to obtain a signal-to-noise ratio of around 10:1. Under these conditions, we obtained an LOQ of 2.10 MBq/mL for HPLC and 2Mbq/mL for TLC. In conclusion, the analytical methods developed in this study comply with EANM recommendations. This therefore allows us to correctly assess the radiochemical purity of 99mTc-cAbVCAM1–5, a new radiotracer targeting inflammation in vulnerable plaques. • 99mTc-cAbVCAM1–5 is a new radiopharmaceutical targeting a marker of inflammation found in vulnerable atheromatous plaques in cardiac diseases. • A validation of the analytical method to evaluate the radiochemical purity (RCP) by HPLC and TLC was carried out. • Specificity, accuracy, precision, linearity, robustness, quantification limit, and range criteria were assessed. • The results demonstrate that the analytical methods are suitable for assessing the RCP of this new radiopharmaceutical. [ABSTRACT FROM AUTHOR]

Purpose: Risk stratification of patients with type 2 diabetes mellitus (T2D) remains suboptimal. We hypothesized that myocardial perfusion entropy (MPE) quantified from SPECT myocardial perfusion images may provide incremental prognostic value in T2D patients independently from myocardial ischemia. Methods: T2D patients with very high and high cardiovascular risk were prospectively included (n = 166, 65 ± 12 years). Stress perfusion defect was quantified by visual evaluation of SPECT MPI. SPECT MPI was also used for the quantification of rest and stress MPE. The primary end point was major adverse cardiac events (MACEs) defined as cardiac death, myocardial infarction (MI), and myocardial revascularization > 3 months after SPECT. Results: Forty-four MACEs were observed during a 4.6-year median follow-up. Significant differences in stress MPE were observed between patients with and without MACEs (4.19 ± 0.46 vs. 3.93 ± 0.40; P ≤.01). By Kaplan-Meier analysis, the risk of MACEs was significantly higher in patients with higher stress MPE (log-rank P ≤ 01). Stress MPE and stress perfusion defect (SSS ≥ 4) were significantly associated with the risk of MACEs (hazard ratio 2.77 and 2.06, respectively, P <.05 for both) after adjustment for clinical and imaging risk predictors as identified from preliminary univariate analysis. MPE demonstrated incremental prognostic value over clinical risk factors, stress test EKG and SSS as evidenced by nested models showing improved Akaike information criterion (AIC), reclassification (global continuous net reclassification improvement [NRI]: 63), global integrated discrimination improvement (IDI: 6%), and discrimination (change in c-statistic: 0.66 vs 0.74). Conclusions: Stress MPE provided independent and incremental prognostic information for the prediction of MACEs in diabetic patients. Trial registration number: NCT02316054 (12/12/2014). [ABSTRACT FROM AUTHOR]

Purpose: To determine whether the assessment of regional wall thickening (WT) in addition to myocardial perfusion from stress supine acquisitions could compensate for the lack of prone acquisition and the corresponding decrease in the diagnostic performance of SPECT myocardial perfusion imaging (MPI) in patients with known or suspected coronary artery disease (CAD). Methods: The study group comprised 41 patients (123 vessels) with known or suspected CAD prospectively recruited for systematic prone and supine 201Tl stress SPECT MPI. The diagnostic performance of SPECT MPI was determined for various image sets including nongated supine images (supine NG), nongated combined prone and supine images (prone and supine NG) and gated supine images, allowing WT evaluation from NG images in addition to perfusion (supine NG + WT) using invasive coronary angiography and fractional flow reserve as the gold standards. Results: The rate of false positives was significantly higher among the supine NG images (20.8%) than among either the prone and supine NG or the supine NG + WT images (3.3% and 2.7%, respectively, P < 0.05 vs. supine NG). Consequently, specificity was higher for the prone and supine NG images than for the supine NG images (96.1% vs. 76.1%, P < 0.01) and was highest for the supine NG + WT images (96.8%, P not significant vs. prone and supine NG), without significant differences in sensitivity (80.0%, 86.6% and 73.3%, respectively, P not significant for all comparisons). Conclusion: The diagnostic performance of supine stress SPECT MPI is improved when WT assessment of ischaemic segments is used as an additional diagnostic criterion to values not significantly different from those with combined prone and supine acquisitions. [ABSTRACT FROM AUTHOR]

Simple Summary: NeoB is undergoing evaluation as a novel theragnostic agent—that is, that it can be employed either for the diagnosis of tumor expressing gastrin-releasing peptide receptor (GRPR) using nuclear imaging, or for the therapy of such GRPR positive tumors using internal radiotherapy. The switch from diagnosis to therapy simply rely on the choice of the radioisotope that is coupled to NeoB. The aim of our study was to investigate—for the first time—the potency of NeoB for tumor therapy once labeled with the beta- emitter Lu-177. This study has been conducted in mice bearing human Gastrointestinal Stromal Tumors (GIST). [177Lu]Lu-NeoB was found to accumulate in the tumor, with only minimal retention in off-target organs. Consequently, mice treated with therapeutic doses of [177Lu]Lu-NeoB (37MBq/week for three weeks) exhibited tumor regression and therefore long term survival in comparison to the control untreated mice. NeoB is a radiotracer targeting the gastrin-releasing peptide receptor (GRPR), a G-protein–coupled receptor expressed in various cancers. The aim of the present study was to evaluate the biodistribution and efficacy of this new therapeutic agent in Gastrointestinal Stromal Tumors (GIST). Eighty-two SCID mice bearing GIST-882 tumors were employed. [177Lu]Lu-NeoB biodistribution was evaluated up to seven days by organ sampling (200 pmol/0.8 MBq, i.v.). For efficacy evaluation, mice received either saline, 400 pmol or 800 pmol of [177Lu]Lu-NeoB (37MBq, 1/w, 3 w, i.v.). SPECT/CT imaging was performed at 24 h, and tumor volume was determined up to 100 days. Elevated and specific [177Lu]Lu-NeoB uptake was found in the GIST tumor, as demonstrated by in vivo competition (19.1 ± 3.9 %ID/g vs. 0.3 ± 0.1 %ID/g at 4h). [177Lu]Lu-NeoB tumor retention (half-life of 40.2 h) resulted in elevated tumor-to-background ratios. Tumor volumes were significantly reduced in both treated groups (p < 0.01), even leading to complete tumor regression at the 400 pmol dose. [177Lu]Lu-NeoB exhibited excellent pharmacokinetics with elevated and prolonged tumor uptake and low uptake in non-target organs such as pancreas. The potential of this new theragnostic agent in different indications, including GIST, is under evaluation in the FIH [177Lu]Lu-NeoB clinical trial. [ABSTRACT FROM AUTHOR]

Recent progress in breast cancer research has led to the identification of Vascular Cell Adhesion Molecule-1 (VCAM-1) as a key actor of metastatic colonization. VCAM-1 promotes lung-metastases and is associated with clinical early recurrence and poor outcome in triple negative breast cancer (TNBC). Our objective was to perform the in vivo imaging of VCAM-1 in mice models of TNBC. The Cancer Genomic Atlas (TCGA) database was analyzed to evaluate the prognostic role of VCAM-1 in TNBC. MDA-MB-231 (VCAM-1+) and control HCC70 (VCAM-1-) TNBC cells were subcutaneously xenografted in mice and VCAM-1 expression was assessed in vivo by single-photon emission computed tomography (SPECT) imaging using 99mTc-cAbVCAM1-5. Then, MDA-MB-231 cells were intravenously injected in mice and VCAM-1 expression in lung metastasis was assessed by SPECT imaging after 8 weeks. TCGA analysis showed that VCAM-1 is associated with a poor prognosis in TNBC patients. In subcutaneous tumor models, 99mTc-cAbVCAM1-5 uptake was 2-fold higher in MDA-MB-231 than in HCC70 (p < 0.01), and 4-fold higher than that of the irrelevant control (p < 0.01). Moreover, 99mTc-cAbVCAM1-5 uptake in MDA-MB-231 lung metastases was also higher than that of 99mTc-Ctl (p < 0.05). 99mTc-cAbVCAM1-5 is therefore a suitable tool to evaluate the role of VCAM-1 as a marker of tumor aggressiveness of TNBC. [ABSTRACT FROM AUTHOR]