Introduction Natural polymeric nanoparticles are favored for their size, high drug-loading capacity, bioavailability, non-toxicity, biocompatibility, and the possibility of versatile surface modifications and functionalization’s. For these reasons, nanocellulose has attracted interest as a potential drug nanocarrier. Labeling nanomaterials with fluorescent molecules has become a popular tool for in vitro autophagy monitoring, nanotoxicological studies, and the development of therapeutic applications. Among several markers, fluorescein isothiocyanate (FITC) stands out primarily for its biocompatibility and direct conjugation chemistry. Purpose This project aims to prepare a controlled-release system suitable for in vivo application based on a fluorescein-labeled polymeric nanocellulose matrix. Material and methods Cellulose nanofibrils (CNF) were produced from sugarcane stalks using a mechanical and chemical process. The nanocompound was FITC-functionalized in three steps, as previously described (Environ. Sci.: Nano, 2019, 6,1516). Briefly. Step 1: 15 mL of 3.7% solid CNF suspension was reacted with 250 mL of epichlorohydrin in the presence of 50 mL of 1.34 M NaOH, under mechanical stirring at 60°C for 2h. The epoxy functionalized CNF was centrifuged at 17,500 crf for 5 minutes and then washed with DI water 3 times. Step 2: The epoxy-functionalized CNF after 24 hours was adjusted to pH 12 with 1.34 M NaOH and reacted with 2.8 mL of NH4OH under mechanical stirring at 60°C for 2h. The amine-functionalized CNF were then centrifuged and washed as described above. Step 3: The amine-functionalized CNF were placed in a Na2B4O7 and NaCl buffer solution for 30 min. A water solution of FITC was prepared by adding 0.07g of FITC isothiocyanate in 50 mL of DI water and stirring for 30 min. 1.05g of NaCl and 2.3g of Na2B4O7 were added to the 1% solids CNF suspension, which was then stirred for 30 min. The FITC solution was then added to the CNF and stirred for 12 hours. Finally, the FITC-tagged materials were centrifuged at 17,500 crf for 5 minutes and washed 10 times with DI water. The final 10 wash waters were saved for fluorescence analysis on a Typhoon fluorescence imaging system. The final product was analyzed by FT-IR. Results FITC conjugation to CNF was confirmed by the presence of C=S stretching at 1,083 cm-1. Final product washing step confirmed the absence of FITC by the fourth portion. Conclusion FITC-CNF was adequately prepared, and it is suitable for the next step involving the tumor cell behavior as uptake and toxicity.

Introduction/Justification The development of radiopharmaceuticals has advanced considerably in recent decades, focusing on molecules capable of transporting radionuclides that emit ionizing radiation, such as alpha (a) and beta (ß) particles or Auger electrons. An important strategy is theranostics, which integrates diagnosis and therapy in a single agent through radionuclides that also emit gamma () or positron (ß+) radiation, enabling real-time, non-invasive monitoring. In this context, imines, amines, semicarbazones, and thiosemicarbazones have attracted interest due to their biological properties and versatile metal coordination behavior. Objectives This work aims to develop a hexadentate bis(imine)-based chelator (H4L) for gallium(III) coordination and to prepare its 67Ga-labeled analogue, followed by characterization and in vitro evaluation for radiopharmaceutical applications. Materials and Methods The ligand H4L was synthesized in three steps affording a red solid in 85% yield. The complex [Ga(HL)] was prepared by reacting H4L with [Ga(acac)3] in methanol under reflux for 6h, yielding a yellow solid in ca. 80% yield. Radiolabeling of H4L with 67GaCl3 was achieved within 15 min at room temperature, with radiochemical purity as confirmed by HPLC and iTLC. To evaluate in vitro stability prior to biological assays, the radiocomplex was incubated in PBS at 37°C and analyzed by HPLC after 1h, 2h, and 24h. The ligands and complexes [Ga(HL)] were characterized by FT-IR, NMR spectroscopy, and ESI-MS. Results Comparison of the FT-IR spectra of the free ligand H4L and the complex [Ga(HL)] shows a shift in the v(C=N) stretching region, indicating coordination to the metal center. The proposed structure was further confirmed by ¹H NMR data, with signal integration consistent with the expected number of protons. ESI-MS analysis in negative ion mode confirming the formation of both species. Radiolabeling of [67Ga(HL)] evaluated by HPLC showed rapid and efficient complex formation, matching the non-radioactive analogue [Ga(HL)]. iTLC analysis showed a single species and no evidence of hydrolyzed gallium species. Radiochemical purity exceeded 95%. In vitro stability studies revealed an increase in one isomer after 1 h of incubation; however, no release of 67GaCl3 was observed up to 24h, indicating high stability and absence of transchelation. Conclusion The chelator H4L was successfully synthesized and coordinated to gallium, yielding [Ga(HL)] and its radioactive analogue [67Ga(HL)] with high radiochemical yield and purity. Structural validation via FT-IR, ¹H NMR, and ES-MS confirmed the metal coordination and integrity of the ligand. Furthermore, in vitro stability studies in PBS at 37°C demonstrated that the radiocomplex remained intact for up to 24 hours without metal dissociation, indicating its suitability for future in vivo assessments. These promising results pave the way for structural optimization through spacer units and subsequent bioconjugation studies for the development of new radiopharmaceuticals.

Therapeutic radioisotopes were first used in clinical practice in 1941 to treat thyroid cancer, using a mixture of 131I/133I produced in a cyclotron. Nowadays, high-purity 131I is still used to treat thyroid disease, but it is produced in nuclear reactors. From the 1980s to the 2010s, new radioisotopes were introduced for cancer treatment, including beta (β) emitter 90Y, 153Sm, and 166Ho. By the end of 2010, 177Lu emerged as a promising radioisotope for theranostic applications, and by 2020, 161Tb was identified as a promising new radioisotope due to its simultaneous β and Auger-electron emission. Also, the alpha emitters 211At, 225Ac, 212Pb, and 213Bi have proven effective in cancer treatment. Requirements for radioisotopes production The production of these radioisotopes depends on specific nuclear reactions requiring either high-energy charged particles or high neutron fluxes. For 225Ac, several methods were tested, one of the oldest is 232Th(p,x)225Ac, >100 MeV. However, this route is controversial because it co-produces 227Ac, a long half-life (21.7 y) alpha emitter, that makes impossible it uses in humans; alternatively 226Ra(p,2n)225Ac ≥ 30 MeV; other possibility is 226Ra(g,n)225Ra (β)225Ac has been in use to produce 225Ac with the higher radionuclide purity, 209Bi(α,2n)211At, but with alpha particles not higher than 29-28 MeV to avoid production to 211Po, 151Eu(3He,5n)149Tb 40-70 MeV. Beyond the production of standard beta-emitting radioisotopes, current research focuses on the 160Gd(n,γ)161Gd(β)161Tb (thermal neutron flux, in the range of 1013 to 1014 n.cm-2.s-1). Reactor and cyclotron production capability in Argentina and Brazil Argentina and Brazil have installed 10 research reactors, but only three of them, RA-3 (10 MW, neutron 1-1.4 × 1014) and RA-10 (30 MW, 1.4-2.5 × 1014 (expected to be critical in 2027), by CNEA, in Argentina, and the IEA-R1 (4.5 MW, 1 × 1014) in Brazil have the capacity to produce of therapeutic radioisotopes in commercial scale. From these, Ra-3 is producing 99Mo, 51Cr, 131I and 177Lu, and 161Tb under R&D production. Currently, the IEA-R1 is not producing radioisotopes, but it is planned to return to the production of 131I and start the 177Lu production in 2026. Furthermore, Brazil has begun construction of the Brazilian Multipurpose Reactor (RMB), which will operate at 30 MW and is scheduled to begin operations in 2032. There are 26 cyclotrons installed in the region, but a limited number can operate above 20 MeV, restricting the production of advanced therapeutic radionuclides. Argentina has the CP-42 (42 MeV), which is in maintenance and returning at the end of 2026, and a new center is planned to operate a 30 MeV Cyclotron in 2029, focusing on 225Ac production for industrial applications. In Brazil, the IPEN is investing in cyclotron-based production of 225Ac via the 225Ra (p,2n)225Ac using its 30 MeV cyclotron. In parallel, IPEN has established partnerships with multinational companies to process and purify 226Ra, supporting a sustainable and scalable 225Ac supply chain.Conclusion: The production and distribution of emerging therapeutic radioisotopes require substantial and specialized human resources, which constrain access in the region. The commissioning of new reactors, particularly RA-10 and the RMB, is expected to significantly enhance regional capabilities, while cyclotron-based production remains largely restricted to conventional medical radionuclides.

Introduction/Justification The development of novel peptide-associated chelators that exhibit greater radiochemical stability compared to classical systems is of great interest in radiopharmaceutical chemistry, especially due to the challenges observed in in vitro and in vivo biological stability studies. Although the molecular development step is complex and laborious, evaluating the feasibility of complexation with radionuclides is fundamental to determining the potential use of these molecules as radiotracers. In this context, the NAQ chelator was developed to promote a stable bond with technetium-99m in the tricarbonyl form, exploiting an amide binding site, in a manner analogous to peptide-histidine interactions, but as a promising alternative. Objectives To evaluate the radiolabeling efficiency of an anti-EGFR peptide modified with the chelating agent NAQ, as well as to investigate the radiochemical purity obtained under different peptide concentrations and pH conditions. Materials and Methods The tricarbonyl-Tc-99m precursor was prepared from a solid mixture of sodium borohydride, potassium carbonate and sodium potassium tartrate under a CO atmosphere, followed by the addition of sodium pertechnetate (∼14.9 mCi) and heating at 80°C for 30 minutes. The anti-EGFR peptide conjugated to the C6 spacer and to NAQ chelator was prepared in 1 mM 20% acetonitrile and aliquoted at 158, 474, and 948 µg/mL. Radiolabeling was performed by the addition of tricarbonyl-Tc-99m (∼9 mCi), followed by heating (70°C, 30 minutes). Quality control of the tricarbonyl precursor (pH 8) and radiolabeled samples were performed by radio-HPLC. A second experiment was conducted with pH adjustment to 6.5, followed by purification in a Sep-Pak C18 cartridge. Autoradiography was performed on 20 µm histological brain sections containing C6 glioblastoma at 15 and 60 minutes of incubation with the purified radiolabeled peptide (10 µL, 105 µCi/mL). After successive washes in water, the slides were dried at room temperature and exposed to a phosphor imaging plate for 10 minutes, followed by reading on a photoluminescence scanner. Results The tricarbonyl-Tc-99m complex exhibited a radiochemical purity of 97 ± 0.4%. The radiolabeled peptides showed radiochemical purity of approximately 68% for concentrations of 158 and 474 µg/mL and 78% for 948 µg/mL. Additional chromatographic peaks were visually observed, mainly at the highest concentration, although not identified. After pH adjustment and purification of the radiolabeled peptide at 158 µg/mL, a radiochemical yield of 76% was obtained, with 7% of the activity retained in the cartridge. Additionally, the preliminary autoradiography study demonstrated accumulation of the radiolabeled peptide in the tumor region, indicating that the peptide's affinity for the target was maintained after conjugation with the chelating agent NAQ; however, further assays are needed to confirm and validate this finding. Conclusion The results indicate that the NAQ chelator shows potential for the radiolabeling of peptides with technetium-99m, although the methodology still needs optimization. Further evaluations involving pH and temperature adjustments and purification strategies are necessary to improve the efficiency and radiochemical purity of the conjugate, enabling its application in future biological studies.

Background/Objectives: Dithiocarbazates (DTCs) and their metal complexes have been studied regarding their property as anticancer activities. In this work, using S-benzyl-5-hydroxy-3-methyl-5-phenyl-4,5-dihydro-1H-pirazol-1-carbodithionate (H2bdtc), we prepared [ReO(bdtc)(Hbdtc)] and [[99mTc]TcO(bdtc)(Hbdtc)] complexes for tumor uptake and animal biodistribution studies. Methods: Re complex was prepared by a reaction of H2bdtc and (NBu4)[ReOCl4], the final product was characterized by IR, 1H NMR, CHN, and MS-ESI. 99mTc complex was prepared by the reaction of H2bdtc and [[99mTc]TcO4− and analyzed by planar and HPLC radiochromatography, and the stability was evaluated against amino acids and plasma. Biodistribution was performed in C57B/6 mice with B16F10 and TM1M implanted tumor. Results: Re is asymmetric coordinated by two dithiocarbazate ligands, one with O,N,S chelation, and the other with N,S chelation; [[99mTc]TcO(bdtc)(Hbdtc)] was prepared with a radiochemical yield of around 93%. The radioactive complex is hydrophobic (LogP = 1.03), stable for 6 h in PBS and L-histidine solution; stable for 1 h in plasma, but unstable in the presence of L-cysteine. Ex vivo biodistribution demonstrated that the compound has a fast and persistent (until 2 h) uptake by the spleen (55.46%), and tumor B16F10 and TM1M uptake is lower than 1%. In vivo SPECT/CT imaging confirmed ex vivo biodistribution, except by heterogenous TM1M accumulation but not in the B16-F10 lineage. Conclusions: H2bdtc proved to be an interesting chelator for rhenium or [99mTc]technetium. The right spleen uptake opened the opportunity to deepen the study of the molecule in this tissue and justifies future studies to identify the reason of heterogenous uptake in TM1M tumor uptake.

Thiosemicarbazones are a class of iminic organosulfur compounds synthesized by condensation reaction between a thiosemicarbazide and an aldehyde or ketone. Such compounds present a wide range of biological activities, either as sole organic compounds or in association with metallic species. The fluorinated pyrazoline cyclic thiosemicarbazones described herein were synthesized from 4,4,4-trifluoro-1-phenyl-1,3-butanedione and three thiosemicarbazides. The reactions resulted in thiosemicarbazones 1, 2, and 3, with 51, 70, and 71% yields, respectively. which were characterized by elemental analysis, FTIR, 1H and 19F{1H} NMR, mass spectrometry and single crystal X-ray diffraction. The spectral data confirm that the thiosemicarbazones are cyclic the both in solid state and solution, as no evidence of ring-chain tautomerism has been observed. Additionally, single-crystal X-ray diffraction studies revealed that the compounds mentioned above crystallized in centrosymmetric space groups, two of them in monoclinic P21/n and the last one in triclinic P . Theoretical free energies of formation were calculated using the DFT methodology, and the results indicate that the ring isomer is significantly more stable than the chain isomer; thus, no ring-chain isomerism is expected to form, in agreement with the experimental data.

Introduction/Justification: Liposomes are microscopic vesicles containing an aqueous core surrounded by a lipid bilayer, enabling lipophilic and hydrophilic drugs to be encapsulated. Due to this characteristic, they have been used as transporters of substances to treat or diagnose diseases, including radiopharmaceuticals. Objectives: This work aims to prepare liposome from phosphatidylserine, encapsulate 99mTc- MDP inside it, and compare murine 4T1 breast cell tumor uptake for 99mTc-MDP and 99mTc-MDP-liposome. Materials and Methods: Liposome was prepared by adding 90 mg of phosphatidylserine in a chloroform/methanol solution at a concentration of (9:1). The solvents were evaporated in a desiccator until the lipids formed a film at the bottom of the vial. The radiopharmaceutical 99mTc-MDP was obtained from the reconstitution of a lyophilized kit with a 99mTcO4- solution, according to radiolabeling instructions. The liposome was reconstituted with saline and 99mTc-MDP was added; the solution was sonicated for 10 min. The purification and encapsulation of percentage were done by size exclusion filtration in an Amicon® 10 kD filter, including two water washes. Murine 4T1 breast cancer cells were grown in RPMI-1640 culture medium supplemented with 10% fetal bovine serum, under 37°C in a humidified atmosphere with 5% CO2 and seed at 5 × 104 cell/well and stood overnight in culture conditions. 99mTc-MDP and 99mTc-MDP-liposome were added to wells, in triplicate, and stood in culture conditions for 15, 30, 60 and 120 min. Culture medium was removed, cells were washed twice with PBS, the cells were detached from the wells, and radioactivity was measured in a gamma counter. The cell internalization percentage was determined by dividing cells counts by a standard sample. Results: The 99mTc-MDP encapsulation in the liposome reached an average of 68 ± 26% (n = 3), determined by size exclusion filtration. In vitro tumor cells uptake for 99mTc-MDP fluctuated between 0.2% during interval time. On the other hand, 99mTc-MDP-liposome tumor cells uptake had 0.7% ± 0.1% (15 min), 0.8 ± 0.2% (30 min) 0.9 ± 0.2% (60 min) and 1.2 ± 0,4 (120 min). Conclusion: The experiments demonstrated the feasibility of liposome production and their use for encapsulate 99mTc-MDP radiopharmaceutical. Loaded 99mTc-MDP-liposome had significantly high tumor uptake compared to 99mTc-MDP alone, demonstrating the effectivity of the phosphatidylserine liposome in delivering radiopharmaceuticals in tumor cells.

Breast cancer remains a pressing public health issue primarily affecting women. Recent research has spotlighted bioactive peptides derived from laminin-111, implicated in breast tumor development. Remarkably, the sequences IKVAV, YIGSR, and KAFDITYVRLKF from the α1, β1, and γ1 chains, respectively, have garnered significant attention. This study aims to assess the potential of these radiolabeled peptides as targeting agents for breast cancer. The three peptides were synthesized using the Fmoc strategy, purified via reversed-phase high-performance liquid chromatography (RP-HPLC), and characterized through mass spectrometry. Iodine-131 ( 131 I) radiolabeling was performed using the chloramine T method, exhibiting high radiochemical yield and stability for [ 131 I]I-YIKVAV and [ 131 I]I-YIGSR. Conversely, [ 131 I]I-KAFDITYVRLKF demonstrated low radiochemical yield and stability and was excluded from the biological studies. The lipophilicity of the compounds ranged from − 2.12 to − 1.10. Serum protein binding assay for [ 131 I]I-YIKVAV and [ 131 I]I-YIGSR reached ≅ 48% and ≅ 25%, respectively. Affinity for breast cancer cells was evaluated using MDA-MB-231 and MCF-7 tumor cell lines, indicating the affinity of the radiopeptides with these tumor cells. Ex vivo biodistribution profiles of the radiopeptides were assessed in the MDA-MB-231 breast tumor animal model, revealing tumor tissue accumulation, supported by a high tumor-to-contralateral muscle ratio and autoradiography. These results signify the effective penetration of YIKVAV and YIGSR into tumor tissue. Therefore, the synthesized α1 and β1 peptide fragments exhibit favorable characteristics as potential breast cancer-targeting agents, promising future exploration as radiopharmaceuticals for breast cancer.

SummaryRadiopharmaceutical research and bioscience or medical applications have changed during the decades in the function of available technologies for radioisotope production and imaging detection technologies. In the 1940s to 1960s year, radioisotopes were supplied by reactor production, such as 131I for thyroid uptake study, 197Hg, 203Hg-chlormerodrin for brain scans, 198Au-colloid for liver scans, and 85Sr-chloride for the bone scans. In the late 1960s, with the development of the gamma camera by Hal Anger, and the 99Mo/99mTc generators by researchers of the Brookhaven National Laboratory, the focus was moved to research and diagnostic application of 99mTc radiopharmaceuticals, and these compounds have been in use until now. In that age, the chemistry of technetium, including the production of different chelators and radiolabeling processes, were developed. Cyclotron-producing radioisotopes for medical application emerged in 1955, and for a long time, it was used to produce gamma-emitting radionuclides such as 67Ga, 111In, and 201Tl. After the development of PET câmera around 1975, positron-emitting radioisotopes started to be produced routinely in cyclotrons, such as 11C, 13N, and 18F, gaining market status for diagnostic applications after Alfred Wolf and colleagues developed the 18F-FDG, around 1978. In the following year, positron-emitting radiometals 68Ga, 64Cu, and 89Zr, began to be produced on a large scale to label molecules with short or long circulation times in the body. The results in the specificity of the diagnostic opened the possibility of using 90Y and 177Lu, both beta-emitting radioisotopes, to label the same molecules for therapeutic purposes; thus, theranostics pair 68Ga or 64Cu/90Y or 177Lu started to be used in nuclear medicine. From the 2010s, true theranostic pairs gain interest, such as 44gSc/47Sc, 64Cu/67Cu, 83Sr/89Sr, 86Y/90Y, 124I/131I, 152Tb/161Tb, and 152Tb/149Tb, stated to be produced and evaluated for clinical applications. All these developments in radioisotope production and imaging systems also boosted the development of molecule radiolabeling processes, mainly through automated systems, to ensure speed, reproducibility, and less exposure to professionals involved in preparing these molecules. Furthermore, several chelating agents have been developed to complex different metals in a simple, effective, and stable way, such as the DOTA, NOTA, HBED molecules, among others.ConclusãoTrends in radioisotopes and radiolabeling methods result from scientific and technological developments in different areas but with congruent purposes. The result is a large number of products that can be chosen by their physical, chemical, biological, or economic characteristics.

Background: Recent advancements in nanomedicine and nanotechnology have expanded the scope of multifunctional nanostructures, offering innovative solutions for targeted drug delivery and diagnostic agents in oncology and nuclear medicine. Nanoparticles, particularly those derived from natural sources, hold immense potential in overcoming biological barriers to enhance therapeutic efficacy and diagnostic accuracy. Papain, a natural plant protease derived from Carica papaya, , emerges as a promising candidate for green nanotechnology-based applications due to its diverse medicinal properties, including anticancer properties. Purpose: This study presents a novel approach in nanomedicine and oncology, exploring the potential of green nanotechnology by developing and evaluating technetium-99m radiolabeled papain nanoparticles (99mTc-P-NPs) 99m Tc-P-NPs) for imaging breast tumors. The study aimed to investigate the efficacy and specificity of these nanoparticles in breast cancer models through preclinical in vitro and in vivo assessments. Methods: Papain nanoparticles (P-NPs) were synthesized using a radiation-driven method and underwent thorough characterization, including size, surface morphology, surface charge, and cytotoxicity assessment. Subsequently, P-NPs were radiolabeled with technetium-99m (99mTc), 99m Tc), and in vitro and in vivo studies were conducted to evaluate cellular uptake at tumor sites, along with biodistribution, SPECT/CT imaging, autoradiography, and immunohistochemistry assays, using breast cancer models. Results: The synthesized P-NPs exhibited a size mean diameter of 9.3 f 1.9 nm and a spherical shape. The in vitro cytotoxic activity of native papain and P-NPs showed low cytotoxicity in HUVEC, MDA-MB231, and 4T1 cells. The achieved radiochemical yield was 94.2 f 3.1% that were sufficiently stable (>= 90%) for 6 h. The tumor uptake achieved in the 4T1 model was 2.49 f 0.32% IA/g at 2 h and 1.51 f 0.20% IA/g at 6 h. In the spontaneous breast cancer model, 1.19 f 0.20% IA/g at 2 h and 0.86 f 0.31% IA/g at 6 h. SPECT/CT imaging has shown substantial tumor uptake of the new nanoradiopharmaceutical and clear tumor visualization. 99m Tc-P-NPs exhibited a high affinity to tumoral cells confirmed by ex vivo autoradiography and immunohistochemistry assays. Conclusion: The findings underscore the potential of green nanotechnology-driven papain nanoparticles as promising agents for molecular imaging of breast and other tumors through SPECT/CT imaging. The results represent a substantial step forward in the application of papain nanoparticles as carriers of diagnostic and therapeutic radionuclides to deliver diagnostic/therapeutic payloads site-specifically to tumor sites for the development of a new generation of nanoradiopharmaceuticals.

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Objetivo: Prospectar a evolução dos pedidos de patentes sobre oncológicos contendo os radioisótopos gálio-68 (68Ga), cobre-64 (64Cu) e zircônio-89 (89Zr) visando a compreensão do desenvolvimento da ciência e da tecnologia na área. Método: Utilizou-se a plataforma ORBIT Intelligence® da empresa QUESTEL® para identificar, extrair, tratar os dados, organizar e disponibilizar as informações tecnológicas em formato de interfaces gráficas das patentes depositadas vigentes nos últimos 20 anos nos principais escritórios de patentes no mundo. Resultado: Foram identificadas para gálio-68, cobre-64 e zircônio-89, respectivamente, 36, 18 e 10 famílias de patentes contendo os termos de busca descritos na metodologia. Em ambos os casos, a China se destaca no número de pedidos de patentes depositados, chegando a depositar 61% do total analisado. Observou-se ainda, que muitos dos documentos analisados foram depositados por universidades, reforçando o conceito da parceria empresa-universidade. Os resultados obtidos apontam que a área do presente estudo continua em crescimento e o entendimento sobre as informações presentes nos documentos de patente possibilitam refletir espaços para intensificar o desenvolvimento de inovações na área oncológica. Conclusões: Os resultados obtidos demonstram a relevância das informações para a gestão no desenvolvimento tecnológico de um país, o qual podem servir como método eficiente para analisar, comparar e monitorar atividades de pesquisa e desenvolvimento em câncer e, ainda, subsidiar os processos de planejamento estratégico das organizações, assim como apoiar as políticas públicas e privadas de saúde.

Na era do Big Data, torna-se premente o compartilhamento aberto de dados em pesquisa, trabalho em rede e a rápida identificação de especialistas em áreas específicas. A Plataforma Lattes é o principal repositório curricular brasileiro, sendo possível extrair diversas informações de pesquisadores, como instituição onde trabalham, linhas de pesquisa, produções científicas, etc. Há limitações na plataforma, como as informações dos especialistas estarem dispostas individualmente e sem um padrão de indexação. Dessa forma, considerando a importância dos radiofármacos para a saúde pública brasileira e mundial, este trabalho objetivou identificar os especialistas mais relevantes em território brasileiro atuando no tema. Utilizou-se como estudo de caso a abordagem quantitativa para análise das informações cadastradas em câncer com especificidade em tecnécio-99m das competências essenciais na área, utilizando a ferramenta computacional ScriptLattes. Os resultados mostraram-se eficientes pela geração de conhecimento científico e tecnológico em vários níveis institucionais, podendo ser replicado em diversas áreas da ciência.

<p>The Kunene Anorthosite Complex (KAC), located in SW Angola, is one of the largest anorthosite structures in the world. Dating from the Mesoproterozoic, its installation process is still not clear. Several mafic and ultramafic outcrops can be found surrounding the KAC. Once considered related with its emplacement, the study of these bodies may help us understand the history of this unique geological feature. While geochronological data show that they are synchronous, or possibly a bit younger, than the embedding granites and migmatites of Paleoproterozoic age, the question arises of whether they are intrusions installed in the host rock or if they are instead recycled remains of older Arch crust. The development of these outcrops in depth provides relevant clues regarding the origin of these bodies and their relationship with the Eburnean (~1.93-2.04 Ga) and Epupa-Namibe (~1.83-1.74 Ga) events. One of these mafic outcrops, designated the Hamutenha outcrop (Huíla Province) exhibits an elongated shape and a NW-SE orientation and is characterized by an internal zonation.  Generally, the innermost part is composed of ultramafic rocks of (mostly harzburgites and dunites), with diorites outcropping in its NW and SE borders. The Hamutenha outcrop was previously identified for potentially bearing Cr, Ni and PGE mineralization.</p><p>Therefore, the aim of this study is two-fold. Firstly, it attempts to determine the development at depth of the mafic body to better understand its origin. Secondly, it tries to clarify the emplacement mechanisms responsible for the potential mineralization and to evaluate the likelihood of its economic potential. Aeromagnetic and ground gravimetric data acquired in the framework of project PLANAGEO (National Geology Plan for Angola) of which the National Laboratory of Energy and Geology (Portugal) was one of the partners, was used to create a magnetic vector model and a density contrast model of the Hamutenha body. These 3D models were interpreted in combination with the detailed geological observations and aeroradiometric data also from the PLANAGEO project, providing new insights on the underground lithological differentiation and geometry of this geological structure.</p>

This study aimed to evaluate the repeatability of brown adipose tissue (BAT) activation measured by [F-18]FDG-PET after beta3-adrenergic stimuli with CL316243 in mice.Methods: Male C57BL/6 mice underwent [F-18]FDG-PET at baseline without stimulation (T0-NS), on three consecutive days after intravenous administration of the selective beta 3-adrenergic agonist CL316243 (T1-CL, T2-CL, T3-CL), and without stimuli after 1 and 2 weeks (T7-NS and T14-NS). The standardized uptake value (SUVmax), BAT metabolic volume (BMV), and total BAT glycolysis (TBG) were measured in each scanning session, with statistical groupwise comparisons by ANOVA and post hoc Tukey test.Results: SUVmax, BMV, and TBG values showed no significant differences between the three PET scans without stimuli, but were significantly higher after CL316243 administration (p < 0.0001). The mean coefficient of variation (CoV) of PET within individuals was 49 % at baseline but only 9 % with pharmacological stimulation.Conclusions: The study demonstrated that administration of the selective beta 3-adrenergic receptor agonist CL316243 (CL) in mice leads to consistent metabolic activation of brown adipose tissue (BAT), as measured by [F-18]FDG-PET. We also demonstrated metabolic activation by repeated pharmacological challenge, without evidence of hysteresis. Thus, the methods used in the current work should serve for further studies on BAT metabolism in experimental animals, with translational value for clinical research.

This study aimed to evaluate the role of positron emission tomography (PET) with [11C]PK11195 and [18F]FDG in the characterization of brown adipose tissue (BAT). Methods: Male C57BL/6 mice were studied with the glucose analogue [18F]FDG (n = 21) and the TSPO mitochondrial tracer [11C]PK11195 (n = 28), without stimulus and after cold (6-9 degrees C) or beta-agonist (CL316243) stimuli. PET studies were performed at baseline and after 21 days of daily treatment with crotamine, which is a peptide described to induce adipocyte tissue browning and to increase BAT metabolism. Tracer uptake (SUVmax) was measured in the interscapular BAT and translocator protein 18 kDa (TSPO) expression was evaluated by immunohistochemistry. Results: The cold stimulus increased [18F]FDG uptake compared to no-stimulus (5.21 & PLUSMN; 1.05 vs. 2.03 & PLUSMN; 0.21, p < 0.0001) and to beta-agonist stimulus (2.65 & PLUSMN; 0.39, p = 0.0003). After 21 days of treatment with crotamine, there was no significant difference in the [18F]FDG uptake compared to the baseline in the no-stimulus group and in the cold-stimulus group, with a significant increase in uptake after CL stimulus (baseline: 2.65 & PLUSMN; 0.39; 21 days crotamine: 4.77 & PLUSMN; 0.81, p = 0.0003). Evaluation of [11C]PK11195 at baseline shows that CL stimulus increases the BAT uptake compared to no-stimulus (4.47 & PLUSMN; 0.66 vs. 3.36 & PLUSMN; 0.68, p = 0.014). After 21 days of treatment with crotamine, there was no significant difference in the [11C]PK11195 uptake compared to the baseline in the no-stimulus group (2.94 & PLUSMN; 0.58, p = 0.7864) and also after CL stimulus (3.55 & PLUSMN; 0.79, p = 0.085). TSPO expression correlated with [11C]PK11195 uptake (r = 0.83, p = 0.018) but not with [18F]FDG uptake (r = 0.40, p = 0.516). Conclusions: [11C]PK11195 allowed the identification of BAT under thermoneutral conditions or after beta3adrenergic stimulation in a direct correlation with TSPO expression. The beta-adrenergic stimulus, despite presenting a lower intensity of glycolytic activation compared to cold at baseline, allowed the observation of an increase in BAT uptake of [18F]FDG after 21 days of crotamine administration. Although some limitations were observed for the metabolic changes induced by crotamine, this study reinforced the potential of using [11C] PK11195 and/or [18F]FDG-PET to monitor the activation of BAT.

Wind-induced fatigue is a major issue for the design of slender high-rise structures. However, there are still few studies focused on this topic, resulting in a lack of practical design procedures for this type of structures. This paper aims to fill this gap by presenting a complete and practical methodology for the wind-induced fatigue life assessment of high-rise towers and its application to a 120 m cable-stayed steel tower composed by a modular lattice. The wind actions were considered as the sum of the quasi-static component according to international codes and a numerically generated, trough an ergodic stochastic process, turbulent component which is based on the Kaimal wind spectrum. Real wind measurements were also taken for a period of 15 months on a nearby MET station which, when compared with the normative scenario, proved to be much less conservative and were not used for the safety analysis. The wind velocities were used as inputs for a nonlinear dynamic analysis from which stress time histories were derived for 10 potentially critical structural details. The damage in each detail was computed through the application of the Rainflow counting algorithm and Palmgren-Miner's damage accumulation law, indicating the connection region between the modules as the critical detail with respect to fatigue damage.

Background: Breast tumor inflammation is an immunological process that occurs mainly by mediation of Tumor-Associated Macrophages (TAM). Aiming for a specific measurement of tumor inflammation, the current study evaluated the potential of Positron Emission Tomography (PET) imaging with [11C](R)-PK11195 to evaluate tumor inflammation in a mammary tumor animal model. Methods: Female Balb/C mice were inoculated with 4T1 cells. The PET imaging with [11C](R)-PK11195 and [18F]FDG was acquired 3 days, 1 week, and 2 weeks after cell inoculation. Results: The [11C](R)-PK11195 tumor uptake increased from 3 days to 1 week, and decreased at 2 weeks after cell inoculation, as opposed to the [18F]FDG uptake, which showed a slight decrease in uptake at 1 week and increased uptake at 2 weeks. In the control group, no significant differences occurred in tracer uptake over time. Tumor uptake of both radiopharmaceuticals is more expressed in tumor edge regions, with greater intensity at 2 weeks, as demonstrated by [11C](R)-PK11195 autoradiography and immunofluorescence with TSPO antibodies and CD86 pro-inflammatory phenotype. Conclusion: The [11C](R)-PK11195 was able to identify heterogeneous tumor inflammation in a murine model of breast cancer and the uptake varied according to tumor size. Together with the glycolytic marker [18F]FDG, molecular imaging with [11C](R)-PK11195 may provide a better characterization of inflammatory responses in cancer.

Located in the Iberian pyrite belt, the Neves–Corvo mine is a world-class massive sulfide deposit and the largest operating mine in Portugal with underground mining down to 1000 m depth focused on massive and stockwork Cu, Zn, Pb rich ores. Gravimetric data have had a leading role in the discovery of the seven known deposits, together with time-domain electromagnetic (TEM) ground data. In this work, we present the results of a 3D constrained gravity inversion carried out with legacy ground gravity data. The 3D gravity inversions were carried out using an updated density database containing approximately 142,000 measurements. A recently constructed 3D geological model based on reprocessed 2D seismic reflection, 3D seismic, TEM and updated geology from detailed surface mapping and drill-hole data, was used to constrain the inversions. The results show multiple high-density anomalies that may indicate the presence of mineralization at depth. These anomalies were therefore cross-checked with holes previously drilled. Approximately 97% of more than 1000 available surface drill-holes located on or at a distance of less than 200 m from the high-density anomalies intersected mineralization. However, gravity anomalies have been drilled in the past and particularly dense black shales or rhyolitic/gabbroic rocks have been intersected. To increase the success of future drilling, gravimetric anomalies have been correlated spatially with high-conductivity TEM zones and strong-amplitude seismic reflections, because igneous rocks usually present weak-to-moderate conductivity and a massive column of black shales presents a seismic signature quite different from that of mineralization. We concluded that some of these locations represent high-quality targets to consider following up with drilling and further exploration.

OBJECTIVES: To identify and evaluate, based on the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and the legislation of the Agencia Nacional de Transportes Terrestres (ANTT - National Agency for Terrestrial Transport), the hazards arising from chemical waste generated in research laboratories in the health area. METHODS: Chemical residues generated in two medical research laboratories of the Faculdade de Medicina da Universidade de Sao Paulo were inventoried, from November 2017 to April 2019, and classified according to the GHS (hazard statements) and the ANTT transport legislation (risk classes), to determine the dangers coming from the respective substances and mixtures. RESULTS: In total, we identified 40 substances or mixtures with classification by the GHS indicating 36 hazard statements, 27 of which related to human health. According to the legislation established by ANTT, we found 16 cases of hazard associated with flammability, 15 cases related to toxicity and 12 cases related to corrosivity. CONCLUSIONS: Chemical residues generated in the laboratories studied are diversified in terms of their hazard characteristics, implying the possibility of exposure to severe risks to workers, students and the environment. The correct identification of these residues is a primary factor for reducing exposure to risks.