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Gallium-68 is a widely used positron-emitting radionuclide in nuclear medicine, traditionally obtained from 68Ge/68Ga generators. However, increasing clinical demand has driven interest in alternative production methods, such as medical cyclotrons equipped with solid targets. This study evaluates the functional equivalence of gallium-68 chloride obtained from cyclotron solid target and formulated to be equivalent to the eluate from a germanium-gallium generator, aiming to determine whether this production method can serve as a reliable alternative for PET radiopharmaceutical applications. Preparations of [68Ga]Ga-PSMA-11 and [68Ga]Ga-DOTATOC, labeled with cyclotron-derived gallium-68 chloride, were subjected to quality control analysis using radio thin layer chromatography and radio high performance liquid chromatography. Subsequently, biodistribution studies were performed in mouse oncological models of expression of PSMA antigen and SSTR receptor to compare uptake of preparations produced with generator and cyclotron-derived isotopes. All tested formulations met the required radiochemical purity specifications. Moreover, tumor accumulation of the radiolabeled compounds was comparable regardless of the isotope source. The results support the conclusion that gallium-68 produced via cyclotron is functionally equivalent to that obtained from a generator, demonstrating its potential for interchangeable use in clinical and research radiopharmaceutical applications.

NIS is a potent iodide transporter encoded by the SLC5A5 gene. Its expression is reduced in papillary thyroid carcinoma (PTC). In this study we analyzed the impact of miR-181a-5p on NIS expression in the context of PTC. We used real-time PCR to analyze the expression of SLC5A5 and miR-181a-5p in 49 PTC/normal tissue pairs. Luciferase assays and mutagenesis were performed to confirm direct binding of miR-181a-5p to the 3′UTR of SLC5A5 and identify the binding site. The impact of modulation of miR-181a-5p using appropriate plasmids on endogenous NIS and radioactive iodine accumulation was verified. We confirmed downregulation of SLC5A5 and concomitant upregulation of miR-181a-5p in PTC. Broadly used algorithms did not predict the binding site of miR-181a-5p in 3′UTR of SLC5A5, but we identified and confirmed the binding site through mutagenesis using luciferase assays. In MCF7 and HEK293-flhNIS cell lines, transfection with mir-181a-expressing plasmid decreased endogenous SLC5A5, whereas silencing of miR-181a-5p increased it. We observed similar tendencies in protein expression and radioactive iodine accumulation. This study shows for the first time that miR-181a-5p directly regulates SLC5A5 expression in the context of PTC and may decrease efficacy of radioiodine treatment. Accordingly, miR-181a-5p may serve as an emerging target to enhance the efficacy of radioactive iodine therapy.

The rapid increase in applications of scandium isotopes in nuclear medicine requires new efficient production routes for these radioisotopes. Recently, irradiations of calcium in cyclotrons by α, deuteron, and proton beams have been used. Therefore, effective post-irradiation separation and preconcentration of the radioactive scandium from the calcium matrix are important to obtain the pure final product in a relatively small volume. Nobias resin was used as a sorbent for effective separation of 44Sc from calcium targets. Separation was performed at pH 3 using a column containing 10 mg of resin. Scandium was eluted with 100 μL of 2 mol L−1 HCl. Particular attention was paid to the reduction of calcium concentration, presence of metallic impurities, robustness and simple automation. 44Sc was separated with 94.9 ± 2.8% yield, with results in the range of 91.7–99.0%. Purity of the eluate was confirmed with ICP-OES determination of metallic impurities and >99% chelation efficiency with DOTATATE, followed by >36 h radiochemical stability of the complex. A wide range of optimal conditions and robustness to target variability and suspended matter facilitates the proposed method in automatic systems for scandium isotope separation and synthesis of scandium-labeled radiopharmaceuticals.

Preclinical and clinical studies have shown that stem cells can promote the regeneration of damaged tissues, but therapeutic protocols need better quality control to confirm the location and number of transplanted cells. This study describes in vivo imaging while assessing reporter gene expression by its binding to a radiolabelled molecule to the respective receptor expressed in target cells. Five mice underwent human skeletal muscle-derived stem/progenitor cell (huSkMDS/PC EF1-HSV-TK) intracardial transplantation after induction of myocardial infarction (MI). The metabolic parameters of control and post-infarction stem progenitor cell-implanted mice were monitored using 2-deoxy-18F-fluorodeoxyglucose ([ 18 F]-FDG) before and after double promotor/reporter probe imaging with 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine ([ 18 F]-FHBG) using positron emission tomography (PET) combined with computed tomography (CT). Standardized uptake values (SUVs) were then calculated based on set regions of interest (ROIs). Experimental animals were euthanized after magnetic resonance imaging (MRI). Molecular [ 18 F]-FHBG imaging of myogenic stem/progenitor cells in control and post-infarction mice confirmed the survival and proliferation of transplanted cells, as shown by an increased or stable signal from the PET apparatus throughout the 5 weeks of monitoring. huSkMDS/PC EF1-HSV-TK transplantation improved cardiac metabolic ([ 18 F]-FDG with PET) and haemodynamic (MRI) parameters. In vivo PET/CT and MRI revealed that the precise use of a promotor/reporter probe incorporated into stem/progenitor cells may improve non-invasive monitoring of targeted cellular therapy in the cardiovascular system.

The aim of this study was to evaluate hypoxia level at various tumor developmental stages and to compare various methods of hypoxia evaluation in pre-clinical CT26 tumor model. Using three methods of hypoxia determination, we evaluated hypoxia levels during CT26 tumor development in BALB/c mice from day 4 till day 19, in 2-3 days intervals. Molecular method was based on the analysis of selected genes expression related to hypoxia (HIF1A, ANGPTL4, TGFB1, VEGFA, ERBB3, CA9) or specific for inflammation in hypoxic sites (CCL2, CCL5) at various time points after CT26 cancer cells inoculation. Imaging methods of hypoxia evaluation included: positron-emission tomography (PET) imaging using [18F]fluoromisonidazole ([18F]FMISO) and a fluorescence microscope imaging of pimonidazole (PIMO)-positive tumor areas at various time points. Our results showed that tumor hypoxia at molecular level was relatively high at early stage of tumor development as reflected by initially high HIF1A and VEGFA expression levels and their subsequent decrease. However, imaging methods (both PET and fluorescence microscopy) showed that hypoxia increased till day 14 of tumor development. Additionally, necrotic regions dominated the tumor tissue at later stages of development, decreasing the number of hypoxic areas and completely eliminating normoxic regions (observed by PET). These results showed that molecular methods of hypoxia determination are more sensitive to show changes undergoing at cellular level, however in order to measure and visualize hypoxia in the whole organ, especially at later stages of tumor development, PET is the preferred tool. Furthermore we concluded, that during development of tumor, two peaks of hypoxia occur.

Viral pneumonia caused by highly infectious SARS-CoV-2 poses a higher risk to older people and those who have underlying health conditions, including Alzheimer’s disease. In this work we present newly designed tacrine-based radioconjugates with physicochemical and biological properties that are crucial for the potential application as diagnostic radiopharmaceuticals. A set of ten tacrine derivatives was synthesized, labelled with gallium-68 and fully characterized in the context of their physicochemical properties. Based on these results, the final two most promising radioconjugates, [68Ga]Ga-NODAGA-Bn-NH(CH2)9Tac and [68Ga]Ga-THP-NH(CH2)9Tac, were selected for biodistribution studies. The latter compound was proven to be a good inhibitor of cholinesterases with significant affinity toward the lungs, according to the biodistribution studies. On the basis of molecular modelling combined with in vitro studies, we unraveled which structural properties of the developed tacrine derivatives are crucial for high affinity toward acetylcholinesterase, whose increased levels in lung tissues in the course of coronavirus disease indicate the onset of pneumonia. The radiopharmaceutical [68Ga]Ga-THP-NH(CH2)9Tac was ultimately selected due to its increased accuracy and improved sensitivity in PET imaging of lung tissue with high levels of acetylcholinesterase, and it may become a novel potential diagnostic modality for the determination of lung perfusion, including in inflammation after COVID-19.

Gallium-68 is a widely used positron-emitting radionuclide in nuclear medicine, traditionally obtained from [sup.68]Ge/[sup.68]Ga generators. However, increasing clinical demand has driven interest in alternative production methods, such as medical cyclotrons equipped with solid targets. This study evaluates the functional equivalence of gallium-68 chloride obtained from cyclotron solid target and formulated to be equivalent to the eluate from a germanium-gallium generator, aiming to determine whether this production method can serve as a reliable alternative for PET radiopharmaceutical applications. Preparations of [[sup.68]Ga]Ga-PSMA-11 and [[sup.68]Ga]Ga-DOTATOC, labeled with cyclotron-derived gallium-68 chloride, were subjected to quality control analysis using radio thin layer chromatography and radio high performance liquid chromatography. Subsequently, biodistribution studies were performed in mouse oncological models of expression of PSMA antigen and SSTR receptor to compare uptake of preparations produced with generator and cyclotron-derived isotopes. All tested formulations met the required radiochemical purity specifications. Moreover, tumor accumulation of the radiolabeled compounds was comparable regardless of the isotope source. The results support the conclusion that gallium-68 produced via cyclotron is functionally equivalent to that obtained from a generator, demonstrating its potential for interchangeable use in clinical and research radiopharmaceutical applications.

Gallium-68 is a widely used positron-emitting radionuclide in nuclear medicine, traditionally obtained from 68Ge/68Ga generators. However, increasing clinical demand has driven interest in alternative production methods, such as medical cyclotrons equipped with solid targets. This study evaluates the functional equivalence of gallium-68 chloride obtained from cyclotron solid target and formulated to be equivalent to the eluate from a germanium-gallium generator, aiming to determine whether this production method can serve as a reliable alternative for PET radiopharmaceutical applications. Preparations of [68Ga]Ga-PSMA-11 and [68Ga]Ga-DOTATOC, labeled with cyclotron-derived gallium-68 chloride, were subjected to quality control analysis using radio thin layer chromatography and radio high performance liquid chromatography. Subsequently, biodistribution studies were performed in mouse oncological models of expression of PSMA antigen and SSTR receptor to compare uptake of preparations produced with generator and cyclotron-derived isotopes. All tested formulations met the required radiochemical purity specifications. Moreover, tumor accumulation of the radiolabeled compounds was comparable regardless of the isotope source. The results support the conclusion that gallium-68 produced via cyclotron is functionally equivalent to that obtained from a generator, demonstrating its potential for interchangeable use in clinical and research radiopharmaceutical applications.Gallium-68 is a widely used positron-emitting radionuclide in nuclear medicine, traditionally obtained from 68Ge/68Ga generators. However, increasing clinical demand has driven interest in alternative production methods, such as medical cyclotrons equipped with solid targets. This study evaluates the functional equivalence of gallium-68 chloride obtained from cyclotron solid target and formulated to be equivalent to the eluate from a germanium-gallium generator, aiming to determine whether this production method can serve as a reliable alternative for PET radiopharmaceutical applications. Preparations of [68Ga]Ga-PSMA-11 and [68Ga]Ga-DOTATOC, labeled with cyclotron-derived gallium-68 chloride, were subjected to quality control analysis using radio thin layer chromatography and radio high performance liquid chromatography. Subsequently, biodistribution studies were performed in mouse oncological models of expression of PSMA antigen and SSTR receptor to compare uptake of preparations produced with generator and cyclotron-derived isotopes. All tested formulations met the required radiochemical purity specifications. Moreover, tumor accumulation of the radiolabeled compounds was comparable regardless of the isotope source. The results support the conclusion that gallium-68 produced via cyclotron is functionally equivalent to that obtained from a generator, demonstrating its potential for interchangeable use in clinical and research radiopharmaceutical applications.

Current treatment protocols for myocardial infarction improve the outcome of disease to some extent but do not provide the clue for full regeneration of the heart tissues. An increasing body of evidence has shown that transplantation of cells may lead to some organ recovery. However, the optimal stem cell population has not been yet identified. We would like to propose a novel pro-regenerative treatment for post-infarction heart based on the combination of human skeletal myoblasts (huSkM) and mesenchymal stem cells (MSCs). huSkM native or overexpressing gene coding for Cx43 (huSKMCx43) alone or combined with MSCs were delivered in four cellular therapeutic variants into the healthy and post-infarction heart of mice while using molecular reporter probes. Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) performed right after cell delivery and 24 h later revealed a trend towards an increase in the isotopic uptake in the post-infarction group of animals treated by a combination of huSkMCx43 with MSC. Bioluminescent imaging (BLI) showed the highest increase in firefly luciferase (fluc) signal intensity in post-infarction heart treated with combination of huSkM and MSCs vs. huSkM alone (p < 0.0001). In healthy myocardium, however, nanoluciferase signal (nanoluc) intensity varied markedly between animals treated with stem cell populations either alone or in combinations with the tendency to be simply decreased. Therefore, our observations seem to show that MSCs supported viability, engraftment, and even proliferation of huSkM in the post-infarction heart.

Hemoglobin (Hb) performs its physiological function within the erythrocyte. Extracellular Hb has prooxidative and proinflammatory properties and is therefore sequestered by haptoglobin and bound by the CD163 receptor on macrophages. In the present study, we demonstrate a novel process of Hb uptake by macrophages independent of haptoglobin and CD163. Unexpectedly, macrophages do not degrade the entire Hb, but instead transfer it to neighboring cells. We have shown that the phenomenon of Hb transfer from macrophages to other cells is mainly mediated by extracellular vesicles. In contrast to the canonical Hb degradation pathway by macrophages, Hb transfer has not been reported before. In addition, we have used the process of Hb transfer in anticancer therapy, where macrophages are loaded with a Hb-anticancer drug conjugate and act as cellular drug carriers. Both mouse and human macrophages loaded with Hb-monomethyl auristatin E (MMAE) effectively killed cancer cells when co-cultured in vitro.