Ana Carolina Marques Ciceri , Laura Eduarda de Oliveira , Ana Luísa Richter , José Antonio Mainardi de Carvalho , Maylla Rodrigues Lucena , Guilherme Wataru Gomes , Maria Stella Figueiredo , Magnun Nueldo Nunes dos Santos , Vera Lúcia Nascimento Blaia-D'Avila , Rodolfo Delfini Cançado , Elvira Maria Guerra-Shinohara , Clóvis Paniz
{"title":"Hematological ratios and cytokine profiles in heterozygous beta-thalassemia","authors":"Ana Carolina Marques Ciceri , Laura Eduarda de Oliveira , Ana Luísa Richter , José Antonio Mainardi de Carvalho , Maylla Rodrigues Lucena , Guilherme Wataru Gomes , Maria Stella Figueiredo , Magnun Nueldo Nunes dos Santos , Vera Lúcia Nascimento Blaia-D'Avila , Rodolfo Delfini Cançado , Elvira Maria Guerra-Shinohara , Clóvis Paniz","doi":"10.1016/j.htct.2025.103845","DOIUrl":"10.1016/j.htct.2025.103845","url":null,"abstract":"<div><h3>Introduction</h3><div>β-Thalassemia is defined by a reduced or complete absence of β-globin chain synthesis in hemoglobin, leading to hemolytic anemia. Heterozygous β-thalassemia, also known as β-thalassemia trait (hBTh), the mildest form of this anemia, typically does not cause symptoms in carriers. However, it may lead to changes in the immune system, including an increase in total leukocyte, neutrophil, and lymphocyte counts.</div></div><div><h3>Objective</h3><div>This study aimed to evaluate various immune and inflammation markers, including neutrophil/lymphocyte, derived neutrophil/lymphocyte, lymphocyte/monocyte, platelet/lymphocyte, neutrophil/platelet ratios, systemic immune-inflammation index, systemic inflammation response index, neutrophil/natural killer cell ratio (NNKR), and inflammatory cytokines in β-thalassemia trait carriers.</div></div><div><h3>Method</h3><div>A retrospective observational study was conducted, including 50 β-thalassemia trait individuals and 100 healthy controls.</div></div><div><h3>Results</h3><div>Leukocyte, neutrophil and reticulocyte counts, and interleukin 6 levels were higher in carriers compared to controls. Notably, the β-thalassemia trait group had increased neutrophil/platelet, neutrophil/lymphocyte and derived neutrophil/lymphocyte ratios, and the systemic immune-inflammation and systemic inflammation response indexes were higher compared to the controls.</div></div><div><h3>Conclusions</h3><div>β-thalassemia trait shows a more pronounced inflammatory profile as indicated by hematological ratios. These ratios, therefore are potentially cost-effective and easily applicable markers for monitoring patients with the β-thalassemia trait.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 3","pages":"Article 103845"},"PeriodicalIF":1.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937903","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}
Andrew Evans Cobbinah , Benedict Sackey , Mina Ofosu , Herbert Ekoe Dankluvi , Stephen Opoku , Ampa Davis Frank
{"title":"Blood storage effect of G6PD on RBC quality","authors":"Andrew Evans Cobbinah , Benedict Sackey , Mina Ofosu , Herbert Ekoe Dankluvi , Stephen Opoku , Ampa Davis Frank","doi":"10.1016/j.htct.2025.103733","DOIUrl":"10.1016/j.htct.2025.103733","url":null,"abstract":"<div><h3>Background</h3><div>The most prevalent metabolic condition of red blood cells, glucose-6-phosphate dehydrogenase (G6PD) deficiency, affects around 35 million people globally. The highest prevalence is seen in tropical and subtropical areas of the eastern hemisphere, where it can affect up to 35 % of the population. G6PD deficiency, the most prevalent enzyme deficit, is not currently tested for in blood products. G6PD deficiency is a genetic factor that influences the quality of stored red blood cells impacting their ability to respond to oxidative stress. This hospital-based cross-sectional study aimed at assessing the prevalence of G6PD deficiency in donor blood and the impact of the enzyme deficiency on red cell indices during storage.</div></div><div><h3>Method</h3><div>A total of 57 blood bags were screened for G6PD deficiency. Red cell indices and blood film comments were investigated on Day 0, Day 7 and Day 14 of storage.</div></div><div><h3>Results</h3><div>Eight out of 57 (14 %) had the G6PD full defect and 86 % (49/57) had no defect. Over the course of 14 days storage, the hemoglobin and red blood cell count significantly decreased in G6PD-deficient blood units with a corresponding significant increase in mean corpuscular volume and red cell distribution width-standard deviation compared to baseline and normal G6PD activity. The blood film comment showed 85.7 % normocytic normochromic, 2.0 % microcytic hypochromic and 12.2 % macrocytic hyperchromic from G6PD-non-deficient donors whereas G6PD-deficient donors had 75 % normocytic normochromic with 12.5 % microcytic hypochromic and 12.5 % macrocytic hypochromic after 2 wk in storage.</div></div><div><h3>Conclusion</h3><div>Red blood cell count and hemoglobin reduce significantly in G6PD-deficient donor units during storage with an associated increased mean corpuscular volume indicating progressive loss of the cellular membrane homeostatic mechanism that could potentially result in further hemolysis during long term storage.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 3","pages":"Article 103733"},"PeriodicalIF":1.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937905","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":"Long-term follow-up results of ruxolitinib as salvage therapy for chronic graft-versus-host disease","authors":"Neslihan Mandaci Sanli , Esen Karakuş","doi":"10.1016/j.htct.2025.103835","DOIUrl":"10.1016/j.htct.2025.103835","url":null,"abstract":"<div><h3>Introduction</h3><div>Chronic graft-versus-host disease poses a significant challenge after allogeneic hematopoietic stem cell transplantation with initial treatment often relying on high-dose steroids. However, managing steroid-refractory disease remains daunting. Recent insights into the mechanisms have unveiled new treatment targets, with ruxolitinib, a selective JAK1/2 inhibitor, emerging as a promising and safe therapy for chronic graft-versus-host disease patients.</div></div><div><h3>Methods</h3><div>This retrospective study describes the long-term outcomes of 23 chronic graft-versus-host disease patients treated with ruxolitinib.</div></div><div><h3>Results</h3><div>Most patients presented with severe chronic graft-versus-host disease (15/23; 65.2%). The overall response rate was 78.3% (18/23) after a median treatment duration of four weeks, with 55.6% (10/18) achieving complete response. At follow-up, 13 of the 18 responders (72.2%) sustained complete remission. Patients had a median of two previous lines of therapy, with a median follow-up of 14 months (range: 2–46 months) after starting ruxolitinib. Of the patients who were responsive to ruxolitinib, median follow-up extended to 26.5 months. Notably, for the patients who were responsive to ruxolitinib, the 1-year, 2-year, and 3-year overall survival was 83.3% (95% CI: 64.2%-102%), 56.1% (95% CI: 30.1%-80.9%), and 33.3% (95% CI: 9.2%-57.4%), respectively. Malignancy relapse occurred in 17.4% (4/23) of patients, with 34.7% (8/23) experiencing cytopenias, albeit mostly mild. Reactivation rates for cytomegalovirus were nil.</div></div><div><h3>Conclusion</h3><div>The long-term follow-up in this study supports ruxolitinib as an effective salvage therapy for chronic graft-versus-host disease with a 78.3% overall response rate and 55.6% complete remission rate. However, large prospective studies are warranted to validate these findings</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 3","pages":"Article 103835"},"PeriodicalIF":1.8,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937904","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}
Jeremy W. Jacobs , Garrett S. Booth , Brian D. Adkins
{"title":"Challenges in diagnosing thrombotic thrombocytopenic purpura","authors":"Jeremy W. Jacobs , Garrett S. Booth , Brian D. Adkins","doi":"10.1016/j.htct.2025.103842","DOIUrl":"10.1016/j.htct.2025.103842","url":null,"abstract":"","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 3","pages":"Article 103842"},"PeriodicalIF":1.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929340","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}
Zahia Esber, Hamza Salam, Shefali Godara, Ayman Soubani
{"title":"Clinical characteristics and outcomes of non-tuberculous mycobacterial pulmonary infections after hematopoietic stem cell transplantation: A retrospective cohort study","authors":"Zahia Esber, Hamza Salam, Shefali Godara, Ayman Soubani","doi":"10.1016/j.htct.2025.103841","DOIUrl":"10.1016/j.htct.2025.103841","url":null,"abstract":"<div><h3>Introduction</h3><div>Non-tuberculous mycobacterial infections are rising as complications of bone marrow transplantation with lung disease being the most common clinical presentation. The identification and management of these infections in hematopoietic stem cell transplantation patients remains underrecognized. This study aims to investigate the clinical characteristics and outcomes in patients with post-transplant pulmonary infections.</div></div><div><h3>Methods</h3><div>The charts of 3,000 adult patients who received transplants over 11 years at the Karmanos Cancer Institute, a tertiary-care cancer center in Detroit, were reviewed. The diagnoses of post-transplant pulmonary non-tuberculous mycobacterial infections of 51 patients were defined as definite, probable or possible based on the American Thoracic Society (ATS) and Centers for Disease Control and Prevention guidelines. The identified organisms were further characterized as rapid- or slow-growing mycobacteria. Clinical characteristics, risk factors, microbiologic data, therapy and outcomes of the patients were collected and analyzed.</div></div><div><h3>Results</h3><div>About half (<em>n</em> = 26; 51%) of the patients were identified with definite pulmonary infection. There was a trend of cardiovascular and pulmonary comorbidities in these patients. The majority (<em>n</em> = 44; 86.3%) were on steroid and immunosuppressive therapy in the setting of graft-versus-host disease. The most common presenting symptoms were a combination of change in cough and worsening shortness of breath. The most common radiologic pattern was nodular infiltrates in 15 (29.4%) patients. <em>Mycobacterium avium complex</em> was identified in 38 (74.5%) patients. The majority of patients with these infections (76.5%) did not receive antimycobacterial therapy. Survival was reported in 42 (82.4%) patients.</div></div><div><h3>Conclusion</h3><div>Outcomes vary significantly among non-tuberculous mycobacterial pulmonary infections based on mycobacterial species, rate of colonization and degree of immunosuppression. The prognosis is overall good due to slow growing mycobacteria. Prospective multicenter studies are required to further guide the management of these patients.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 3","pages":"Article 103841"},"PeriodicalIF":1.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929338","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}
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}