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Abstract Background Beyond the use of conventional short-lived PET radionuclides, there is a growing interest in tracking larger biomolecules and exploring radiotheranostic applications. One promising option for imaging medium-sized molecules and peptides is ⁵⁵Co (T₁/₂ = 17.5 h, β⁺ = 76%), which enables imaging of new and already established tracers with blood circulation of several hours. Additionally, ⁵⁵Co can be paired with the Auger-Meitner emitter 58mCo (T₁/₂ = 9 h, 100% IC) for radiotheranostic applications. Here we report on 55Co production via the 58Ni(p,α)55Co reaction channel using pressed 58Ni and Mg matrix targets. Results This set up is capable to produce and isolate 240 ± 20 MBq [55Co]Co+ 2 (80% RCY) with 4 ml 0.25 M HEPES at 35 min post End Of Bombardment for 3 h, 25 µA protons irradiation. The RNP of the eluate is 99.98 ± 0.014% as measured 2 h & 17 h post EOB. AMA was determined to 1.5 ± 0.5 GBq/µmol [55Co]Co-DOTA at EOB. Mg dissolves rapidly in the acid mixture, leaving behind a porous, sponge-like Ni matrix increasing the surface area of the Ni and therefore accelerating the dissolution. Conclusion We present a novel, simple, and rapid method to produce ⁵⁵Co with pressed ⁵⁸Ni/Mg matrix targets enabling faster target fabrication and dissolution. By using a simple hydraulic press, mechanically stable target coins useful for solid target irradiation are fabricated within 5 min and can be dissolved in 10 min at room temperature. The foils remain intact after irradiation and can endure irradiation conditions providing sufficient activity (> 200 MBq) for clinical doses. The method presented here using Mg as a support metal for fixation of the actual target material into target coins is applicable for other target combinations as well. Using Mg as a support metal is suitable due to its thermal conductivity, low activation, minimal impact on purification chemistry, softness, ductility, and rapid dissolution in acid.

Abstract Background Parkinson's disease is a neurodegenerative disorder that is characterized by a degeneration of the dopaminergic system. Dopamine transporter (DAT) positron emission tomography (PET) imaging has emerged as a powerful and non-invasive method to quantify dopaminergic function in the living brain. The PET radioligand, [18F]FE-PE2I, a cocaine chemical derivative, has shown promising properties for in vivo PET imaging of DAT, including high affinity and selectivity for DAT, excellent brain permeability, and favorable metabolism. The aim of the current study was to scale up the production of [18F]FE-PE2I to fulfil the increasing clinical demand for this tracer. Results Thus, a fully automated and GMP-compliant production procedure has been developed using a commercially available radiosynthesis module GE TRACERLab FX2 N. [18F]FE-PE2I was produced with a radiochemical yield of 39 ± 8% (n = 4, relative [18F]F− delivered to the module). The synthesis time was 70 min, and the molar activity was 925.3 ± 763 GBq/µmol (250 ± 20 Ci/µmol). The produced [18F]FE-PE2I was stable over 6 h at room temperature. Conclusion The protocol reliably provides a sterile and pyrogen–free GMP-compliant product.

Abstract Background The Affibody molecule, ABY-025, has demonstrated utility to detect human epidermal growth factor receptor 2 (HER2) in vivo, either radiolabelled with indium-111 (111In) or gallium-68 (68Ga). Using the latter, 68Ga, is preferred due to its use in positron emission tomography with superior resolution and quantifying capabilities in the clinical setting compared to 111In. For an ongoing phase II study (NCT05619016) evaluating ABY-025 for detecting HER2-low lesions and selection of patients for HER2-targeted treatment, the aim was to optimize an automated and cGMP-compliant radiosynthesis of [68Ga]Ga-ABY-025. [68Ga]Ga-ABY-025 was produced on a synthesis module, Modular-Lab PharmTracer (Eckert & Ziegler), commonly used for 68Ga-labelings. The radiotracer has previously been radiolabeled on this module, but to streamline the production, the method was optimized. Steps requiring manual interactions to the radiolabeling procedure were minimized including a convenient and automated pre-concentration of the 68Ga-eluate and a simplified automated final formulation procedure. Every part of the radiopharmaceutical production was carefully developed to gain robustness and to avoid any operator bound variations to the manufacturing. The optimized production method was successfully applied for 68Ga-labeling of another radiotracer, verifying its versatility as a universal and robust method for radiosynthesis of Affibody-based peptides. Results A simplified and optimized automated cGMP-compliant radiosynthesis method of [68Ga]Ga-ABY-025 was developed. With a decay corrected radiochemical yield of 44 ± 2%, a radiochemical purity (RCP) of 98 ± 1%, and with an RCP stability of 98 ± 1% at 2 h after production, the method was found highly reproducible. The production method also showed comparable results when implemented for radiolabeling another similar peptide. Conclusion The improvements made for the radiosynthesis of [68Ga]Ga-ABY-025, including introducing a pre-concentration of the 68Ga-eluate, aimed to utilize the full potential of the 68Ge/68Ga generator radioactivity output, thereby reducing radioactivity wastage. Furthermore, reducing the number of manually performed preparative steps prior to the radiosynthesis, not only minimized the risk of potential human/operator errors but also enhanced the process’ robustness. The successful application of this optimized radiosynthesis method to another similar peptide underscores its versatility, suggesting that our method can be adopted for 68Ga-labeling radiotracers based on Affibody molecules in general. Trial registration: NCT, NCT05619016, Registered 7 November 2022, https://clinicaltrials.gov/study/NCT05619016?term=HER2&cond=ABY025&rank=1

Abstract Background In vivo monitoring of cell biodistribution using positron emission tomography (PET) provides a quantitative non-invasive method to further optimize cell therapies and related new developments in the field. Our group has earlier optimized and evaluated the in vitro properties of two radiotracers,[89Zr]Zr-(oxinate)4 and [89Zr]Zr-DFO-NCS, for the radiolabelling of different cell types. Here, we performed a microPET study to assess the in vivo biodistribution of cells in rats using these two radiotracers. Human decidual stromal cells (hDSC) and rat macrophages (rMac) were radiolabelled with [89Zr]Zr-(oxinate)4 or [89Zr]Zr-DFO-NCS. Rats were intravenously injected with radiolabelled cells, and the in vivo biodistribution was monitored with microPET/CT imaging for up to day 7. Organ uptake was evaluated and presented as a percentage of injected activity per gram tissue (%IA/g) and total absorbed organ doses (mSv/MBq). Results The biodistribution in vivo showed an immediate uptake in the lungs. Thereafter, [89Zr]Zr-(oxinate)4 labelled cells migrated to the liver, while the signal from [89Zr]Zr-DFO-NCS labelled cells lingered in the lungs. The differences in the in vivo behaviour for the same cell type appeared related to the radiotracer labelling. After 24 h, [89Zr]Zr-(oxinate)4 labelled cells had over 70% higher liver uptake for both hDSC and rMac compared to [89Zr]Zr-DFO-NCS labelled cells, whereas [89Zr]Zr-DFO-NCS labelled cells showed over 60% higher uptake in the lungs compared to [89Zr]Zr-(oxinate)4 labelled cells. This difference in both lung and liver uptake continued until day 7. Dosimetry calculations showed a higher effective dose (mSv/MBq) for [89Zr]Zr-DFO-NCS compared to [89Zr]Zr-(oxinate)4, for both cell types. Although the bone uptake was higher for [89Zr]Zr-(oxinate)4 labelled cells, the prolonged uptake in the lungs contributed to a significant crossfire to bone marrow resulting in a higher bone dose. Conclusion The [89Zr]Zr-DFO-NCS labelled cells suggest a prolonged accumulation in the lungs, while [89Zr]Zr-(oxinate)4 suggests quicker clearance of the lungs followed by accumulation in the liver. Accumulation of radiolabelled cells in the liver corresponds to other cell-tracking methods. Further studies are required to determine the actual location of the [89Zr]Zr-DFO-NCS labelled cell.

Abstract Background Expanding therapeutic possibilities have improved disease-related prospects for breast cancer patients. Pathological analysis on a tumor biopsy is the current reference standard biomarker used to select for treatment with targeted anticancer drugs. This method has, however, several limitations, related to intra- and intertumoral as well as spatial heterogeneity in receptor expression as well as the need to perform invasive procedures that are not always technically feasible. Main body In this narrative review, we focus on the current role of molecular imaging with contemporary radiotracers for positron emission tomography (PET) in breast cancer. We provide an overview of diagnostic radiotracers that represent treatment targets, such as programmed death ligand 1, human epidermal growth factor receptor 2, polyadenosine diphosphate-ribose polymerase and estrogen receptor, and discuss developments in therapeutic radionuclides for breast cancer management. Conclusion Imaging of treatment targets with PET tracers may provide a more reliable precision medicine tool to find the right treatment for the right patient at the right time. In addition to visualization of the target of treatment, theranostic trials with alpha- or beta-emitting isotopes provide a future treatment option for patients with metastatic breast cancer.

Cell therapy is an integral modality of regenerative medicine. Macrophages are known for their sensitivity to activation stimuli and capability to recruit other immune cells to the sites of injury and healing. In addition, the route of administration can impact engraftment and efficacy of cell therapy, and modern neuro-interventional techniques provide the possibility for selective intra-arterial (IA) delivery to the central nervous system (CNS) with very low risk. The effects of radiolabelling and catheter transport on differentially activated macrophages were evaluated. Furthermore, the safety of selective IA administration of these macrophages to the rabbit brain was assessed by single-photon emission computed tomography/computed tomography (SPECT/CT) and ultra-high-field (9.4 T) magnetic resonance imaging (MRI). Cells were successfully labeled with ( 111 In)In-(oxinate) 3 and passed through a microcatheter with preserved phenotype. No cells were retained in the healthy rabbit brain after IA administration, and no adverse events could be observed either 1 h ( n = 6) or 24 h ( n = 2) after cell administration. The procedure affected both lipopolysaccharide/gamma interferon (LPS/IFNγ) activated cells and interleukin 4 (IL4), interleukin 10 (IL10)/transforming growth factor beta 1 (TGFβ1) activated cells to some degree. The LPS/IFNγ activated cells had a significant increase in their phagocytotic function. Overall, the major impact on the cell phenotypes was due to the radiolabeling and not passage through the catheter. Unstimulated cells were substantially affected by both radiolabeling and catheter administration and are hence not suited for this procedure, while both activated macrophages retained their initial phenotypes. In conclusion, activated macrophages are suitable candidates for targeted IA administration without adverse effects on normal, healthy brain parenchyma.

Metastatic castration-resistant prostate cancer is today incurable. Conventional imaging methods have limited detection, affecting their ability to give an accurate outcome prognosis, and current therapies for metastatic prostate cancer are insufficient. This inevitably leads to patients relapsing with castration-resistant prostate cancer. Targeting prostate-specific antigens whose expression is closely linked to the activity in the androgen receptor pathway, and thus the pathogenesis of prostate cancer, is a possible way to increase specificity and reduce off-target effects. We have humanized and evaluated radioimmunoconjugates of a previously murine antibody, m5A10, targeting PSA intended for theranostics of hormone-refractory prostate cancer. The humanized antibody h5A10 was expressed in mammalian HEK293 cells transfected with the nucleotide sequences for the heavy and light chains of the antibody. Cell culture medium was filtered and purified by Protein G chromatography, and the buffer was changed to PBS pH 7.4 by dialysis. Murine and humanized 5A10 were conjugated with p-SCN-Bn-CHX-A”-DTPA. Surface plasmon resonance was used to characterize the binding to PSA of the immunoconjugates. Immunoconjugates were labeled with either indium-111 or lutetium-177. Biodistribution studies of murine and humanized 5A10 were performed in mice with LNCaP xenografts. 5A10 was successfully humanized, and in vivo targeting showed specific binding in xenografts. The results thus give an excellent platform for further theranostic development of humanized 5A10 for clinical applications.

By using solid targets in medical cyclotrons, it is possible to produce large amounts of 68GaCl3. Purification of Ga3+ from metal ion impurities is a critical step, as these metals compete with Ga3+ in the complexation with different chelators, which negatively affects the radiolabeling yields. In this work, we significantly lowered the level of iron (Fe) impurities by adding ascorbate in the purification, and the resulting 68GaCl3could be utilized for high-yield radiolabeling of clinically relevant DOTA-based tracers. 68GaCl3 was cyclotron-produced and purified with ascorbate added in the wash solutions through the UTEVA resins. The 68Ga eluate was analyzed for radionuclidic purity (RNP) by gamma spectroscopy, metal content by ICP-MS, and by titrations with the chelators DOTA, NOTA, and HBED. The 68GaCl3eluate was utilized for GMP-radiolabeling of the DOTA-based tracers DOTATOC and FAPI-46 using an automated synthesis module. DOTA chelator titrations gave an apparent molar activity (AMA) of 491 ± 204 GBq/µmol. GMP-compliant syntheses yielded up to 7 GBq/batch [68Ga]Ga-DOTATOC and [68Ga]Ga-FAPI-46 (radiochemical yield, RCY ~ 60%, corresponding to ten times higher compared to generator-based productions). Full quality control (QC) of 68Ga-labelled tracers showed radiochemically pure and stable products at least four hours from end-of-synthesis.

The development of Environmental and Sustainability Education (ESE) in pre-service teacher education in Canada has shown slow but steady progress over the past 40 years. A detailed history of how individuals and groups have influenced its praxis does not yet exist (Elliott & Inwood, 2019, p. 37). This paper attends to the experiences of six teacher educators/graduate students who have been composing their lives in different landscapes in relation to ESE. We employ collaborative autoethnography as our research methodology. Together, we are involved in the process of telling, retelling, and reliving our stories of who we are in relation to ESE. We also pay deep attention to the resonances echoed across our experiences and curate our forward-looking thoughts for/with the future of ESE. We hope to expand current ESE with a more holistic and sustainable approach, which includes integrating place-based wisdom with environmental education; collaborating with material presences not as resources but as partners for multispecies' flourishing; and sustaining the intergenerational reverberations of familial and cultural practices and quantitative literacy.

Introduction: Colorectal cancer (CRC) is one of the main causes of deaths worldwide. Early detection and diagnosis of its precursor lesion, the polyp, is key to reduce its mortality and to improve procedure efficiency. During the last two decades, several computational methods have been proposed to assist clinicians in detection, segmentation and classification tasks but the lack of a common public validation framework makes it difficult to determine which of them is ready to be deployed in the exploration room. Methods: This study presents a complete validation framework and we compare several methodologies for each of the polyp characterization tasks. Results: Results show that the majority of the approaches are able to provide good performance for the detection and segmentation task, but that there is room for improvement regarding polyp classification. Discussion: While studied show promising results in the assistance of polyp detection and segmentation tasks, further research should be done in classification task to obtain reliable results to assist the clinicians during the procedure. The presented framework provides a standarized method for evaluating and comparing different approaches, which could facilitate the identification of clinically prepared assisting methods. [ABSTRACT FROM AUTHOR]

Introduction: Interval cancer (IC) is an important quality indicator in colorectal cancer (CRC) screening. Previously, we found that fecal immunochemical test (FIT) ICs are more common in women, older age, right-sided tumors, and advanced stage. Here, we extended our existing stage IV patient cohort with clinicopathological and molecular characteristics, to identify factors associated with FIT-IC. Methods: Logistic regression models were fit to identify variables associated with the odds of having a stage IV FIT-IC. Multivariate models were corrected for gender, age, and location. Results: A total of 292 screen-detected (SD) CRCs and 215 FIT-IC CRCs were included. FIT-IC CRC had 5 fold higher odds to be a neuroendocrine (NET) tumor and 2.5 fold higher odds to have lymphovascular invasion. Interestingly, some variables lost significance upon accounting for location. Thus, tumor location is a critical covariate that should always be included when evaluating factors related to FIT-IC. Conclusions: We identified NETs and lymphovascular invasion as factors associated with increased odds of having a stage IV FIT-IC. Moreover, we highlight the importance of tumor location as a covariate in evaluating FIT-IC related factors. More research across all stages is needed to clarify how these insights might help to optimize the Flemish CRC screening program. [ABSTRACT FROM AUTHOR]

Objective: Investigation of the anterior and posterior ethmoidal arteries on computed tomography (CT) scans of the sinuses before and during surgery is important, especially for inexperienced surgeons. The aim of this study was to examine the anatomical characteristics of the posterior ethmoid artery in Vietnamese and the distance from the posterior ethmoid artery to the anterior ethmoid artery and the skull base on CT scan. Methods: A cross-sectional study was conducted involving patients aged =18 years who underwent CT scan imaging at the Ear, Nose and Throat Hospital of Ho Chi Minh City from February 2023 to July 2023. Results: There were 100 patients in this study, of whom 51% (51/100) were female and 49% (49/100) were male. Patient ages ranged from 20 to 84 years. Their average age was 40.92±14.65 years. The distance on CT scan between the posterior and anterior ethmoidal arteries was 13.98±1.95 mm (9.3 to 18.6 mm). This distance in males was significantly higher than female (p=0.001). However, there is no difference in this distance between the left and right side (p=0.67). The distance between the posterior ethmoid artery and skull base ranged from 0 to 5.4 mm. The average distance between the posterior ethmoidal artery and skull base on CT scan was 0.95±0.94 mm. The diameter of the posterior ethmoid artery was 0.57-0.91 mm. The average diameter of the posterior ethmoidal artery on CT scan was 0.76±0.09 mm. Conclusion: The characteristics of the posterior ethmoid artery should be considered when examining the CT scan. Distance from the posterior ethmoid This study provides useful information on the characteristics of the posterior ethmoid artery on CT scans, which can be applied in endoscopic sinus surgery and skull base surgery. [ABSTRACT FROM AUTHOR]

This study aims to propose an efficient Machine Learning (ML) model, namely Gradient Boosting Regression Trees (GBRT), to predict apartment prices considering the fluctuation of construction material prices and the annual inflation index. For developing the ML model, 480 apartments in Vinh City (Vietnam) were considered. The input parameters employed while training the ML model were the area of the apartments, the number of bedrooms/restrooms, the apartment class, nearby health or education services, investment potential, and parking, whereas the apartment price was the output of the model. The results show that the GBRT model predicts the apartment price accurately with a high value of 0.997 and a small RMSE of 0.26. Additionally, the obtained a20-index is very high, almost 1.0. Finally, a practical graphical user interface was developed to facilitate the prediction of the apartment price in terms of usability. [ABSTRACT FROM AUTHOR]