YASMIN RIBEIRO MACHADO, Maria Clara de Lima PIRES, Leandro de Oliveira COSTA
{"title":"TERAPIAS ALVO PARA O CÂNCER DE MAMA TRIPLO NEGATIVO: POTENCIAL DA TRODELVY® (SACITUZUMABE GOVITECANO)","authors":"YASMIN RIBEIRO MACHADO, Maria Clara de Lima PIRES, Leandro de Oliveira COSTA","doi":"10.1016/j.htct.2025.103818","DOIUrl":"10.1016/j.htct.2025.103818","url":null,"abstract":"<div><h3>Sumário</h3><div>1. Introdução 2. Desenvolvimento 2.1. Câncer de Mama Triplo-Negativo 2.2. Terapia Alvo com sacituzumabe govitecano 2.3. Efeitos Adversos 3. Conclusão.</div></div><div><h3>Resumo</h3><div>O câncer de mama triplo-negativo (CMTN) é um subtipo agressivo de câncer de mama, caracterizado pela ausência de receptores hormonais de estrogênio (ER) e progesterona (PR), além da não expressão do receptor HER2. Devido à falta de alvos terapêuticos específicos, o CMTN possui opções limitadas de tratamento, sendo a quimioterapia convencional, a principal abordagem. Neste sentido, tendo em vista a exigência por métodos inovadores, esse estudo visa relatar a eficácia da terapia com sacituzumabe govitecano no tratamento do CMTN, com foco em avaliar os dados disponíveis sobre os resultados clínicos e a eficácia dessa terapêutica. Para isso, foi realizada uma revisão integrativa da literatura em bases indexadas, como o PubMed, Scielo, e Lilacs, selecionando estudos clínicos no período de 2011 a 2025. O CMTN, é conhecido por sua alta taxa de proliferação e metástase precoce, dificultando o tratamento e reduzindo a sobrevida dos pacientes. Diante disso, a ausência de alvos moleculares bem definidos limita as opções terapêuticas, tornando essencial a busca por novas abordagens, como terapias imunológicas e terapias alvo. Sob esse âmbito, tem se destacado a terapia alvo com sacituzumabe govitecano, que é um conjugado de anticorpo monoclonal direcionado ao Trop-2, acoplado a um agente quimioterápico (SN-38). Esse mecanismo permite que o fármaco seja internalizado na célula tumoral, liberando o quimioterápico diretamente no interior da célula cancerígena, reduzindo danos às células saudáveis. Estudos clínicos demonstraram melhoria na sobrevida livre de progressão e sobrevida global quando comparado às terapias convencionais, sendo uma opção promissora para pacientes com CMTN metastático. Apesar dos benefícios, a terapia com sacituzumabe govitecano pode causar efeitos adversos, sendo os mais comuns a neutropenia, que aumenta o risco de infecções, podendo necessitar do uso de fatores estimuladores de colônias de granulócitos (G-CSF) para recuperar a contagem de neutrófilos e a diarreia. Assim, conclui-se que o acompanhamento clínico rigoroso é essencial para minimizar complicações e garantir a segurança do tratamento.</div></div><div><h3>Conclusão</h3><div>A terapia com Sacituzumabe Govitecano representa um avanço significativo no tratamento do câncer de mama triplo-negativo, oferecendo uma alternativa eficaz para pacientes refratários às terapias convencionais. Ao agir diretamente nos receptores Trop-2, a medicação melhora os prognósticos e apresenta uma eficácia superior às abordagens tradicionais. No entanto, desafios como os efeitos adversos, especialmente neutropenia e diarreia, devem ser gerenciados adequadamente. Além disso, o alto custo do tratamento restringe seu acesso no Brasil, apesar da aprovação pela ANVISA. Estratégias como o uso de G","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103818"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mariana Almeida Figueira , Joaldo Garcia Arruda , Victor Maia Miranda , Pedro Paulo Corbi , Luiz Antônio Sodré Costa , Fabio Luiz Navarro Marques , Victor Marcelo Deflon
{"title":"A BORON COMPLEX DESIGNED FOR FLUORINE-18 LABELING AIMING FOR PET IMAGING APPLICATION","authors":"Mariana Almeida Figueira , Joaldo Garcia Arruda , Victor Maia Miranda , Pedro Paulo Corbi , Luiz Antônio Sodré Costa , Fabio Luiz Navarro Marques , Victor Marcelo Deflon","doi":"10.1016/j.htct.2025.103789","DOIUrl":"10.1016/j.htct.2025.103789","url":null,"abstract":"<div><h3>Introduction/Justification</h3><div>Positron emission tomography (PET) is a rapidly expanding clinical modality worldwide due to the availability of compact medical cyclotrons and automated chemistry for the production of radiopharmaceuticals. Despite the availability of various positron-emitting radionuclides such as carbon-11 [11C], fluorine-18 [18F], and gallium-68 [68Ga], 18F has gained more importance and preeminence in research and diagnostic nuclear medicine due to its appropriate half-life of 110 min. Currently, 18F-fluorodeoxyglucose [18F]FDG is the most used radiopharmaceutical for the detection of various neurological disorders and cancer diseases. Since standard 18F-fluorination methods to form carbon-fluorine bonds have some limitations, such as low yield and the requirement for harsh reaction conditions, inorganic approaches, including the formation of boron-fluorine-18 bonds, have the potential to give high specific activities at room temperature, forming a bond that is stable in vivo. The boron complex is planned to be used in fluorine-18 labeling, aiming to develop a potential radiopharmaceutical for PET.</div></div><div><h3>Objectives</h3><div>This work aims to produce a new boron compound with a trivalent and tetradentate chelating agent, relatively stable in air and in solution, but reactive in the presence of fluoride ions, to form an inert fluorinated species, aiming for its use in fluor-18 labeling and application in PET imaging.</div></div><div><h3>Materials and Methods</h3><div>A tetradentate trivalent chelator, named 3-((bis-(2-hydroxyethyl)amino)methyl)-2-hydroxy-5-methylbenzaldehyde (abbreviated as H3L), was synthesized as previously described and used to prepare a neutral tetracoordinated boron complex, named [BL], by its equimolar quantitative reaction with boric acid in acetonitrile under reflux conditions overnight, as a white solid, which was filtered, dried, and characterized. By spectroscopic monitoring, the formation of a new species was observed in methanol solution from [BL] and NaF, supposedly forming Na[BFL]. The structures of the [BL] molecule and of the [BFL]1- anion were theoretically calculated by DFT methods.</div></div><div><h3>Results</h3><div>The H3L free ligand and the boron complex were satisfactorily characterized by diverse techniques, including mass spectrometry, FT-IR, UV-Vis, and NMR spectroscopies (1H, 13C, and 11B) and single crystal X-ray diffraction. The complex [BL] was formed upon deprotonation of three hydroxyl groups in the free ligand, whose oxygens formed the coordination sphere together with the nitrogen atom. The coordination compound has a distorted tetrahedral coordination geometry, which might favor the formation of the bond between the boron atom and the fluoride ion, which is a strong nucleophile, by weakening the boron-nitrogen bond but keeping the oxygen donor atoms strongly coordinated to the boron center.</div></div><div><h3>Conclusion</h3><div>Both, the free lig","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103789"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ACHADOS METABÓLICOS PÓS VACINAÇÃO PARA COVID-19 EM PET-CT COM 18F-FDG","authors":"Antonio Eduardo Santos Stroppa","doi":"10.1016/j.htct.2025.103772","DOIUrl":"10.1016/j.htct.2025.103772","url":null,"abstract":"<div><h3>Introdução/Justificativa</h3><div>O processo de vacinação em massa contra a COVID-19 levou ao surgimento, nos exames de PET-CT com 18F-FDG, de hipermetabolismo glicolítico nos linfonodos de drenagem regional do sítio de injeção. Nesse contexto, em função da dificuldade de diferenciação diagnóstica desses achados reacionais com lesões secundárias linfonodais, podem ser solicitados exames complementares confirmatórios (como seguimento por Ultrassonografia ou Tomografia) ou iniciados tratamentos baseados em eventuais falso-positivos. Nesse sentido, estudos e revisões passaram a indicar o reagendamento de PET-CT com 18F-FDG para até 6 semanas após a imunização. O presente estudo se justifica pela necessidade de uma melhor caracterização de tais efeitos morfometabólicos da imunização contra o SARS-CoV-2, observados no PET-CT com 18F-FDG, o que pode otimizar a diferenciação de achados caracteristicamente reacionais de outras hipóteses.</div></div><div><h3>Objetivos</h3><div>O presente estudo tem o propósito de descrever os padrões de imagem observados ao PET-CT com 18F-FDG associados à resposta inflamatória que surge após a vacinação, com diferentes tipos de imunizantes contra o SARS-CoV-2, bem como investigar a incidência de linfonodos de drenagem regional com hipermetabolismo glicolítico de natureza reacional relacionados, alterações de forma dos mesmos, além da duração e magnitude de tais alterações.</div></div><div><h3>Materiais e Métodos</h3><div>Foram avaliados, retrospectivamente, os exames de PET-CT com 18F-FDG e prontuários eletrônicos de 87 pacientes vacinados contra COVID-19, no ano de 2021, na cidade do Rio de Janeiro, sobretudo os imunizantes ChAdOxnCoV-19 (AstraZeneca – 36 pacientes) e Coronavac (Sinovac – 16 pacientes), quanto à forma do linfonodo de drenagem regional (normal x alterado), seus níveis metabólicos ao PET-CT, sua natureza (falso positivo para malignidade x reacional pós-vacina x normal) e a relação desses achados com o tempo desde a imunização, a idade e o tipo de imunizante.</div></div><div><h3>Resultados</h3><div>Houve o surgimento de graus variados de hipermetabolismo glicolítico em linfonodos de drenagem regional após a vacinação contra a COVID-19, em 27,6 % dos pacientes, com relação inversa do SUVmax ao número de dias desde a imunização (rs= -0,590 e p-valor ≤ 0,001 para o sítio de injeção; rs = -0,416 e p-valor = 0,013 para o linfonodo axilar) e à idade do imunizado (rs= -0,376; p-valor = 0,024).; evidencia ainda que tais achados foram extremamente infrequentes após 4 semanas de imunização. Ademais, os resultados do estudo demonstram menor incidência de achados metabólicos pós-vacinais (6,3%), naqueles pacientes vacinados com o imunizante Coronavac, sem nenhum achado equívoco para natureza reacional inflamatória ou neoplásica, para este grupo.</div></div><div><h3>Conclusão</h3><div>O presente estudo demonstrou o surgimento de achados metabólicos reacionais pós-vacinais em PET-CT com 18F-FDG em pacientes imun","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103772"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leonardo Yumoto Carvalheira , Danielle Viera Sobral , Flávio Lopes Alves , Carolina de Aguiar Ferreira , Leonardo Lima Fuscaldi , Luciana Malavolta
{"title":"SYNTHESIS, CHARACTERIZATION, AND RADIOLABELING OF MODIFIED EGFR-TARGETING PEPTIDES: POTENTIAL THERANOSTIC AGENTS?","authors":"Leonardo Yumoto Carvalheira , Danielle Viera Sobral , Flávio Lopes Alves , Carolina de Aguiar Ferreira , Leonardo Lima Fuscaldi , Luciana Malavolta","doi":"10.1016/j.htct.2025.103794","DOIUrl":"10.1016/j.htct.2025.103794","url":null,"abstract":"<div><h3>Introduction/Justification</h3><div>Cancer remains one of the leading causes of mortality worldwide. Consequently, efforts to overcome the limitations of conventional therapies have increasingly focused on molecularly targeted treatments, with particular emphasis on peptides due to their anti-tumorigenic properties and high affinity for receptors overexpressed in tumors. Peptides designed to inhibit intracellular signaling pathways play a key role in molecularly targeted therapies, often focusing on receptors such as the Epidermal Growth Factor receptor (EGFr), which is overexpressed in many solid tumors. As targeting biomolecules, these peptides can also serve as carriers for radionuclides, enabling both molecular imaging and targeted radionuclide therapy.</div></div><div><h3>Objectives</h3><div>This study aimed to develop modified peptides with high affinity for EGFr, thereby enabling their potential application as theranostic molecules.</div></div><div><h3>Materials and Methods</h3><div>Anti-EGFr peptides were modified by incorporating two different spacers—hexa-aminocaproic acid (C6) or dodeca-aminocaproic acid (C12)—and by adding the chelating agent DOTA. These peptides were synthesized using the Fmoc/tBu strategy for peptide synthesis. Cleavage from the resin was performed using a reagent mixture with a high concentration of trifluoroacetic acid (reagent K). Subsequently, the peptides underwent characterization and purification through high-performance liquid chromatography (HPLC) and mass spectrometry. A preliminary radiolabeling assay of DOTA-C6-anti-EGFR was conducted using cyclotron-produced yttrium-86 (⁸⁶Y) in a NaOAc buffer (pH 5.5). The radiochemical reaction was carried out at 95°C for 30 min, followed by purification through a Sep-Pak C18 cartridge to determine the radiolabeling yield.</div></div><div><h3>Results</h3><div>The peptides DOTA-C6-anti-EGFr and DOTA-C12-anti-EGFr were successfully synthesized, with yields of 33.8% and 3.3%. HPLC and mass spectrometry analyses confirmed the efficiency of the synthesis, cleavage, and purification processes, as evidenced by the molecular masses corresponding to the expected peptides. Preliminary radiolabeling data for DOTA-C6-anti-EGFr with ⁸⁶Y demonstrated a radiochemical yield of approximately 96.5%.</div></div><div><h3>Conclusion</h3><div>The modified peptides targeting EGFr were successfully synthesized, characterized, and purified. The significantly lower yield obtained for the C12 spacer suggests that peptides incorporating the C6 spacer are more viable for further development. Moreover, the high radiochemical yield of DOTA-C6-anti-EGFR highlights its potential for future radiochemical and theranostic applications, warranting further investigation.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103794"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ROMULO SANTANA OSTHUES, Elba Cristina Sá de Camargo ETCHEBEHERE, Barbara Juarez AMORIM, Carmino Antonio DE SOUZA, Larissa Mansano DE SOUZA, Amira Al DERGHAM
{"title":"DIGITAL HEALTH LITERACY AND CANCER MISINFORMATION/DISINFORMATION IN BRAZIL: IMPLICATIONS FOR SCIENTIFIC DISSEMINATION IN NUCLEAR MEDICINE AND ONCOLOGY","authors":"ROMULO SANTANA OSTHUES, Elba Cristina Sá de Camargo ETCHEBEHERE, Barbara Juarez AMORIM, Carmino Antonio DE SOUZA, Larissa Mansano DE SOUZA, Amira Al DERGHAM","doi":"10.1016/j.htct.2025.103819","DOIUrl":"10.1016/j.htct.2025.103819","url":null,"abstract":"<div><h3>Summary</h3><div>The study investigates digital health literacy and misinformation/disinformation related to cancer, with an emphasis on understanding the obstacles to scientific dissemination about nuclear technologies applied in the Theranostic model. This model, which integrates diagnosis and treatment through radiopharmaceuticals, has the potential to significantly improve the care of Oncology patients by directing radiation precisely to tumor tissue, thereby minimizing side effects. However, the complexity of innovations such as those present in Theranostics poses challenges for scientific dissemination, especially in a scenario where misinformation/disinformation, denialism, and pseudoscience are becoming increasingly frequent, influencing the public perception of the safety and efficacy of medical approaches. Various studies indicate that low health literacy can lead to the spread of erroneous information and an increase in prejudice and distrust, negatively impacting adherence to modern therapies and communication between physicians and patients. The literature review shows that media companies frequently prioritize sensationalist and stereotyped topics about nuclear technology, while reliable information is neglected. Moreover, research indicates disparities in digital health literacy among different population groups, highlighting the need for new strategies to formulate educational campaigns and scientific dissemination actions that strengthen access to evidence-based information, thereby contributing to the improvement of patients' quality of life and the reinforcement of health systems. In view of this scenario, the application of an online questionnaire, based on the adapted version of the eHealth Literacy Scales (eHEALS), is imperative to measure the hypotheses regarding individuals’ ability to seek, understand, and use reliable information about cancer and the nuclear technologies involved in diagnostic and therapeutic procedures with radiopharmaceuticals, as well as to identify the main channels and sociodemographic factors that may influence the dissemination of misleading content.</div></div><div><h3>Conclusion</h3><div>As a result of the literature review, it was found necessary to improve the population's digital health literacy and combat misinformation/disinformation related to cancer, especially regarding the use of nuclear technology for diagnostic and therapeutic purposes — particularly through the radiopharmaceuticals used in Nuclear Medicine. The application of the proposed questionnaire in the Brazilian scenario will allow the identification of barriers and gaps in understanding the benefits of the Theranostic model, providing support for the development of educational strategies and scientific dissemination actions promoted by the Knowledge Dissemination team of CEPID CancerThera. These actions are fundamental to popularize access to knowledge, reduce the negative impact of misinformation/disinformation, and","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103819"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Angélica Christiny Ribeiro de Toledo , Daniel Paixão Pequeno , Juliana Carron , Karla Cristina Gaspar , Carmen Silvia Passos Lima , Clarissa Rosalmeida Dantas , Gustavo Jacob Lourenço
{"title":"ASSOCIAÇÃO ENTRE SINTOMAS DE DEPRESSÃO E UMA VARIANTE NO GENE DA CHAPERONA ERP29 ASSOCIADA A PROCESSOS INFLAMATÓRIOS EM PACIENTES COM CÂNCER DE CABEÇA E PESCOÇO","authors":"Angélica Christiny Ribeiro de Toledo , Daniel Paixão Pequeno , Juliana Carron , Karla Cristina Gaspar , Carmen Silvia Passos Lima , Clarissa Rosalmeida Dantas , Gustavo Jacob Lourenço","doi":"10.1016/j.htct.2025.103769","DOIUrl":"10.1016/j.htct.2025.103769","url":null,"abstract":"<div><h3>Introdução/Justificativa</h3><div>O câncer de cabeça e pescoço (CCP) é um problema de saúde global, frequentemente acompanhado de reações emocionais, incluindo a depressão. Genes que regulam as vias de resposta inflamatória ao estresse desempenham um papel importante nos processos depressivos. O gene ERP29 codifica uma proteína chaperona envolvida no enovelamento e secreção de proteínas no retículo endoplasmático. Estudos conduzidos pelo nosso grupo demonstraram que a supressão do ERP29 em linhagens de células de tumores de cabeça e pescoço está associada ao aumento da expressão de genes das vias MAPK e Akt, conhecidas por seu envolvimento em processos inflamatórios. Além disso, uma variante genética de base única (SNV) no ERP29 (rs7114, A>G) foi associada a um maior risco de desenvolvimento de CCP e à redução da expressão do gene. No entanto, a relação dessa SNV com os sintomas depressivos ainda não foi estabelecida.</div></div><div><h3>Objetivos</h3><div>O presente estudo teve como objetivos: 1) investigar se os sintomas depressivos em pacientes com CCP estão associados a características clínicas e do tumor, e 2) avaliar a relação entre os genótipos da SNV ERP29 rs7114 e os sintomas depressivos.</div></div><div><h3>Materiais e Métodos</h3><div>Foram avaliados 70 pacientes com CCP (57 homens, 13 mulheres, idade média de 60 anos, 59 tabagistas e 54 etilistas) atendidos até dois anos após o diagnóstico no Hospital de Clínicas da UNICAMP. Os sintomas depressivos foram avaliados por meio do Inventário de Depressão de Beck (BDI-II) que contém 21 questões abordando aspectos como humor depressivo, culpa, ideação suicida, isolamento social, alteração na imagem corporal, distúrbios do sono, fadiga e perda de libido. Cada item é pontuado de zero (ausência de sintoma) a três (sintoma grave) e a soma total reflete a gravidade dos sintomas depressivos. Os genótipos da SNV ERP29 rs7114 (AA, AG ou GG) foram identificados por meio da reação em cadeia da polimerase em tempo real com sondas TaqMan (Life Technologies) e os reagentes do kit TaqMan Universal PCR Master Mix (Applied Biosystems), seguindo as recomendações do fabricante. O significado estatístico das diferenças entre os grupos foi calculado por meio do teste de Mann-Whitney com os resultados apresentados em mediana e intervalo interquartil (IQR).</div></div><div><h3>Resultados</h3><div>As características clínicas dos pacientes (sexo, estado civil, tabagismo e etilismo) e os aspectos do tumor (localização e estágio TNM) não influenciaram os sintomas depressivos desses pacientes com CCP. No entanto, observamos que os pacientes mais jovens (< 60 anos) apresentaram sintomas depressivos mais intensos (22 (IQR: 18,0) vs. 16 (IQR: 14), p = 0,02). Além disso, pacientes com os genótipos AG ou GG da SNV rs7114 (A>G) no ERP29 tiveram pontuações mais altas de sintomas depressivos em comparação com aqueles com o genótipo AA (28 (IQR: 14,5) vs. 18 (IQR: 13), p = 0,02).</div></div><div><h3>Conclusão","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103769"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexandre D´Agostini Zottis , Júlia Luiz Agostinho , Eduardo Ricardo Santana , Karina Bettega Felipe , Maria Julia Mendes dos Santos Chiquito
{"title":"NANOPARTÍCULAS SUPERPARAMAGNÉTICAS DE ÓXIDO DE FERRO RECOBERTAS POR COPOLIÉSTER FUNCIONALIZADAS PARA APLICAÇÕES BIOMÉDICAS","authors":"Alexandre D´Agostini Zottis , Júlia Luiz Agostinho , Eduardo Ricardo Santana , Karina Bettega Felipe , Maria Julia Mendes dos Santos Chiquito","doi":"10.1016/j.htct.2025.103808","DOIUrl":"10.1016/j.htct.2025.103808","url":null,"abstract":"<div><h3>Introdução/Justificativa</h3><div>O câncer engloba mais de 100 tipos de doenças malignas caracterizadas pelo crescimento descontrolado de células, que podem invadir tecidos adjacentes ou se espalhar para outras partes do corpo. Há décadas, as nanopartículas magnéticas (NPMs) de óxido de ferro vêm sendo estudadas por apresentarem grande potencial para aplicações biomédicas, especialmente na oncologia, no uso de agentes de contraste para imagem por ressonância magnética no realçamento de contraste negativo nos tecidos com a presença de tumores e não tumorais, em magneto hipertermia para destruição seletiva de células cancerosas e atuando no transporte vetorizado de fármacos quimioterápicos. Independente de suas aplicações biomédicas, para evitar a aglomeração das NPMs em células, tecidos e órgãos, que pode levar a embolismos, é essencial recobri-las com materiais biocompatíveis e não citotóxicos. Poliésteres derivados de lactonas e macrolactonas, como o copoliéster poli(globalide-co-ε-caprolactona) (PGlCL), têm sido explorados devido à sua biocompatibilidade, hidrofilicidade e biodegradabilidade.</div></div><div><h3>Objetivos</h3><div>Este trabalho teve como objetivo a modificação e a funcionalização do copoliéster PGICL com cisteína, a fim de atingir três objetivos associados a funcionalização das NPMs, que garantirão sua aplicação em nanomedicina, tais como: a) melhorar sua hidrofilicidade (diminuindo sua cristalinidade) para que seja carreado com mais facilidade no meio intracelular; b) permitir que grupos amina e tiol sejam pontos de ancoragem para constituírem partes de ligantes com receptores de superfície celular, tais como o ácido fólico (AF) que só são expressos em células tumorais e c) possibilitar a ligação desses grupos químicos em sistemas de \"drug-delivery\" com o análogo do AF, o quimioterápico metotrexato (MTX) para o tratamento de câncer de mama. Neste estudo, o PGlCL foi modificado com cisteína (PGlCL-Cys) e utilizado para recobrir NPMs de óxido de ferro (Fe3O4 - magnetita), visando futuramente em um segundo passo, a funcionalização com AF e MTX em aplicações como vetorização ativas em sistemas como “drug-delivery” e a posteriori, em ensaios in vitro de radiosensibilização em células de câncer de mama.</div></div><div><h3>Materiais e Métodos</h3><div>Soluções de Fe³⁺ e Fe²⁺ em HCl. Sob refluxo, adicionaram-se H₂O aquecida, NH₄OH (30mL, pH10, 90°C), PGICL em etanol. Agitou-se 45min, purificou-se com imã, lavou-se e armazenou as NPMs.</div></div><div><h3>Resultados</h3><div>A caracterização físico-química das NPMs recobertas com PGlCL-Cys foi realizada por espectroscopia no infravermelho, confirmando a presença de bandas características da cisteína (ligações C-S-C em 715,21 cm⁻¹ e C-N em 1573,1 cm⁻¹) e do recobrimento das NPMs (bandas de deformação angular da ligação Fe- O em 635,63 cm⁻¹ e ∼590 cm⁻¹, correspondentes aos sítios octaédricos e tetraédricos da magnetita, respectivamente). A Microscopia Eletrônica de Transmissão ","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103808"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"DIRECT COMPARISON BETWEEN 18F-FDG PET/CT AND 18F-PSMA PET/CT IN RADIOIODINE-REFRACTORY DIFFERENTIATED THYROID CARCINOMA PATIENTS","authors":"Murilo Oliveira Cerci, Juliana Chaves Garcia, Simone Kuba, Natália Tobar, Carmino Antônio de Souza, Denise Engelbrecht Zantut-Wittmann, Celso Dario Ramos","doi":"10.1016/j.htct.2025.103792","DOIUrl":"10.1016/j.htct.2025.103792","url":null,"abstract":"<div><h3>Introduction/Justification</h3><div>Differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy and generally has a good prognosis when properly treated. However, approximately 5-15% of cases become refractory to radioiodine therapy (rRIT), limiting diagnostic and therapeutic options and significantly impacting patient survival. Recent studies have demonstrated prostate-specific membrane antigen (PSMA) uptake in positron emission tomography/computed tomography (PET/CT) scans of advanced DTC, suggesting its potential as a diagnostic imaging target and possibly opening new avenues for theranostic approaches.</div></div><div><h3>Objectives</h3><div>To compare 18F-PSMA and 18F-fluorodeoxyglucose (18F-FDG) PET/CT scans of patients with rRIT DTC.</div></div><div><h3>Materials and Methods</h3><div>This cross-sectional study included 21 patients with rRIT DTC and locoregional or distant metastases. All patients underwent both 18F-FDG PET/CT and 18F-PSMA PET/CT scans. Uptake intensity was assessed using the maximum standardized uptake value (SUVmax), and lesion location was categorized as thyroid bed, cervical, thoracic, and abdominal lymph nodes, lungs, liver, and bones. The median SUVmax (range) was calculated for both radiotracers.</div></div><div><h3>Results</h3><div>Both radiotracers detected lesions in all patients. The number of patients with active disease identified by 18F-FDG PET/CT and 18F-PSMA PET/CT, respectively, in each region was: thyroid bed (6 vs. 5), cervical lymph nodes (15 vs. 15), thoracic lymph nodes (11 vs. 11), abdominal lymph nodes (3 vs. 0), lungs (16 vs. 15), bones (4 vs. 6), and liver (1 vs. 1). In five patients, 18F-FDG identified more affected regions than 18F-PSMA, while in three patients, the opposite was observed. The median SUVmax was 24.2 (5.6–80.9) for 18F-FDG and 17.3 (4.1–73.3) for 18F-PSMA. In 12 patients (57.14%), the SUVmax of 18F-PSMA was higher than that of 18F-FDG.</div></div><div><h3>Conclusion</h3><div>Both radiotracers demonstrated uptake in at least some lesions in all rRIT DTC patients. Uptake intensity varied among lesions, with some showing higher 18F-FDG uptake and others higher 18F-PSMA uptake, suggesting a potential complementary role for these tracers in this disease. 18F-PSMA demonstrated a higher SUVmax than 18F-FDG in more than half of the patients, indicating that, in selected cases, PSMA-labeled theranostic approaches may be a viable option.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103792"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hadila da Silva Veras Sousa, Vivian Naomi Horita, Matheus Yung Perin, Daniel Naves Araújo Teixeira, Joyce Gruenwaldt, Eduardo Baldon Pereira, Carlos Takahiro Chone, Gustavo Jacob Lourenço, Ligia Traldi Macedo, Carmen Silvia Passos Lima
{"title":"PLATINUM-BASED CHEMORADIOTHERAPY AS DEFINITIVE TREATMENT IN ADVANCED SQUAMOUS CELL CARCINOMA OF HEAD AND NECK IN REAL-WORLD SETTING","authors":"Hadila da Silva Veras Sousa, Vivian Naomi Horita, Matheus Yung Perin, Daniel Naves Araújo Teixeira, Joyce Gruenwaldt, Eduardo Baldon Pereira, Carlos Takahiro Chone, Gustavo Jacob Lourenço, Ligia Traldi Macedo, Carmen Silvia Passos Lima","doi":"10.1016/j.htct.2025.103782","DOIUrl":"10.1016/j.htct.2025.103782","url":null,"abstract":"<div><h3>Introduction/Justification</h3><div>Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent malignant tumor globally, and over 60% of patients present locoregionally advanced tumors. Platinum-based chemoradiotherapy is a widely adopted treatment for patients with unresectable locoregionally advanced HNSCC, those ineligible for surgery and those refusing surgery due to potential sequelae. While this approach has yielded favorable results in developed countries, its effectiveness in real-world settings in developing countries remains underexplored. Investigating treatment outcomes in this context is essential for optimizing oncologic care.</div></div><div><h3>Objectives</h3><div>To assess the toxicity profile, tumor response, event-free survival (EFS), and overall survival (OS) in patients with locoregionally advanced HNSCC treated with definitive platinum-based chemoradiotherapy.</div></div><div><h3>Materials and Methods</h3><div>This retrospective study included 233 patients treated at the Oncology Service of the General Hospital of University of Campinas (UNICAMP). Inclusion criteria encompassed patients aged 18 or older, with an Eastern Cooperative Oncology Group (ECOG) of 2 or lower, who underwent radiotherapy (RT) combined with either weekly or every-three-weeks administration of cisplatin (CDDP) or carboplatin (Carbo) as definitive treatment. Grade 3 or 4 adverse events were documented according to the National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0) standards. Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Survival outcomes were estimated with the Kaplan-Meier method, and statistical comparisons were performed using the log-rank test and Cox proportional hazards regression for univariate and multivariate analyses.</div></div><div><h3>Results</h3><div>The median age of patients enrolled in study was 60 years. Most enrolled subjects were males, active or former smokers and drinkers, had good performance status and comorbidities, and presented moderately differentiated and advanced tumors. Tumors were equally distributed in oral cavity, pharynx and larynx. Half of the patients developed grade 3 or 4 toxicities, with nausea/vomiting and nephrotoxicity being more frequently observed in the RT + CDDP group, while anemia and neutropenia were predominant in the RT + Carbo group. A total of 75% of patients achieved either complete or partial tumor response, with no significant impact from the treatment regimen. The two-year EFS and OS rates were 43.3% and 66.0%, respectively. Poor prognosis was associated with active smoking, ECOG performance status ≥ 2, stage IV disease, and treatment with RT + Carbo. Patients with these characteristics had an approximately twofold higher risk of presenting relapse and disease progression leading to death.</div></div><div><h3>Conclusion</h3><div>This study highlights RT and CDDP as the most effective definitive treatment for pati","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103782"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fernanda Ferreira Mendonça , Marycel Figols de Barboza , Solange Amorim Nogueira , Ana Claudia Camargo Miranda , Jorge Mejia , Leonardo Lima Fuscaldi , Luciana Malavolta
{"title":"BIODISTRIBUTION OF A TECHNETIUM-99M RADIOLABELED PEPTIDE DERIVED FROM LAMININ-111 IN A BREAST CANCER MODEL","authors":"Fernanda Ferreira Mendonça , Marycel Figols de Barboza , Solange Amorim Nogueira , Ana Claudia Camargo Miranda , Jorge Mejia , Leonardo Lima Fuscaldi , Luciana Malavolta","doi":"10.1016/j.htct.2025.103783","DOIUrl":"10.1016/j.htct.2025.103783","url":null,"abstract":"<div><h3>Introduction/Justification</h3><div>Breast cancer is a significant public health concern, ranking as the second most common tumor type among women. According to the World Health Organization (WHO), more than 14 million people develop breast cancer annually, with this number projected to rise to over 21 million by 2030. Studies have shown that biologically active peptides derived from laminin-111 can regulate gene expression in breast cancer-derived cells, among which the YIGSR peptide is of particular interest. Peptides designed to inhibit intracellular signaling pathways fall within the realm of molecular targeted therapies, which commonly focus on receptors overexpressed in tumors.</div></div><div><h3>Objectives</h3><div>This study aimed to evaluate the biological behavior of the HYIGSR peptide, a laminin-111 derivative, radiolabeled with technetium-99m ([99mTc]Tc(CO)3), in a biodistribution assay using both control and breast cancer model mice.</div></div><div><h3>Materials and Methods</h3><div>The HYIGSR peptide was radiolabeled using the tricarbonyl method, which enabled labeling at the histidine residue with the organometallic aqua-ion [99mTc(H2O)3(CO)3]+, abbreviated as [99mTc]Tc(CO)3. The reaction was carried out by reducing [99mTc]TcO4- under 1 atm of CO for 30 min at 70°C, followed by incubation with approximately 148 MBq of [99mTc]Tc(CO)3 for 30 min at 85°C. The radiochemical purity of [99mTc]Tc(CO)3-HYIGSR was assessed using TLC-SG strips with 0.9% NaCl as the eluent. A breast cancer animal model was established by inoculating female Balb/c nude mice with 1 × 10⁷ MDA-MB-231 breast cancer cells. After 30 days, in vivo (molecular imaging) and ex vivo biodistribution studies were performed. The radiolabeled peptide was intravenously administered to both healthy and tumor-bearing female Balb/c nude mice, and ex vivo biodistribution analysis was conducted at 1 and 3 h post-injection. Molecular imaging of healthy mice was acquired via planar scintigraphy using a single-hole collimator on a Discovery VH clinical gamma camera, with an acquisition time of 5 min and a geometric magnification of 9 × . All animal experiments adhered to local ethical guidelines for animal research (Protocol number: CEUA – HIAE 6015-24).</div></div><div><h3>Results</h3><div>The radiolabeling process using [99mTc]Tc(CO)3 was successfully standardized, yielding [99mTc]Tc(CO)3-HYIGSR with a radiochemical purity of 95.53 ± 1.19% (n = 5). Ex vivo biodistribution analysis in female Balb/c nude mice (n = 4) demonstrated rapid blood clearance over time, with increased uptake in the kidneys. Minimal accumulation of the radiolabeled peptide was observed in the heart, spleen, lungs, and muscle, with the percentage of the injected dose per gram (%ID/g) remaining below 5%. However, high uptake was observed in the liver, stomach, intestine, and thyroid. In tumor-bearing mice, tumor uptake was measured at 0.58 ± 0.25 %ID/g, with a tumor-to-muscle ratio of 1.54 ± 0.14. Pr","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103783"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}