Hematology, Transfusion and Cell Therapy最新文献

{"title":"EFFECTS OF A CONVENTIONAL CHELATOR-MODIFIED ANTI-INTEGRIN PEPTIDE ON GLIOBLASTOMA CELL PROLIFERATION AND MIGRATION","authors":"Juliana Carron , Gabriella Fraiji Melo , Flávio Lopes Alves , João Ernesto Carvalho , Ana Lucia Tasca Gois Ruiz , Leonardo Lima Fuscaldi , Luciana Malavolta , Carmen Silvia Passos Lima","doi":"10.1016/j.htct.2025.103761","DOIUrl":"10.1016/j.htct.2025.103761","url":null,"abstract":"<div><h3>Introduction/Justification</h3><div>Glioblastoma (GB) is the most aggressive brain tumor, with high morbidity and mortality rates. The overall survival of GB patients is only 14 months, not improved by the traditional or latest therapeutic options, as surgical resection, temozolomide chemoradiation or gefitinib. FAPESP-founded “Cancer Innovation Center with Emphasis on Metals and Theranostics” (CancerThera) is dedicated to the development of new metallopharmaceuticals and radiopharmaceuticals for tumor diagnosis and treatment. Among these developments, an anti-integrin peptide modified by a conventional spacer (C6) and chelator (DOTA) was evaluated as a potential treatment of GB. Overexpressed in GB, integrins are transmembrane proteins that play essential roles in cell proliferation and migration. Therefore, integrin inhibition may be a potential targeted therapy for GB patients.</div></div><div><h3>Objectives</h3><div>The study aimed to evaluate the effects of the DOTA-C6-anti-integrin peptide on GB cell lines proliferation and migration, as an initial step for GB theranostic development.</div></div><div><h3>Materials and Methods</h3><div>The anti-proliferative activity of the DOTA-C6-anti-integrin peptide (0.01 nM - 100 µM) was evaluated in human GB (U87, U118, and U251), murine GB (GL261), and non-tumoral cell lines (HaCaT), by considering the cell amounts at baseline and 48h after exposure (two untreated control groups). Cells were fixed with 50% trichloroacetic acid and stained with sulforhodamine B. Spectrophotometric absorbance was performed at 540nm in a microplate reader. Cell migration was assessed in U118, U251, and Gl261 cells treated with the DOTA-C6-anti-integrin peptide (1 µM - 100 µM) using the wound-healing assay. Wound cells were photographed immediately (0h) and after 24h. Images were analyzed by the ImageJ software (National Institutes of Health). For statistical analysis, samples did assume normal distribution in Shapiro-Wilk's test, thus we used t test to compare the groups using SPSS 21 software (SPSS Incorporation). Resultados: At the tested concentration range, the DOTA-C6-anti-integrin peptide did not affect proliferation of GB and HaCaT cell lines. In U118 cells, we observed that treatment with the DOTA-C6-anti-integrin peptide had no effect on cell migration at any of the tested concentrations. In contrast, in U251 cells, the treatment significantly inhibited migration compared to untreated cells at a concentration of 100 µM (p = 0.03). In Gl261 cells, the treatment significantly inhibited migration compared to untreated cells at concentrations of 1 µM and 0.1 µM (p = 0.04).</div></div><div><h3>Conclusion</h3><div>Despite the lack of anti-proliferative effect, the DOTA-C6-anti-integrin peptide inhibited migration in GB cell lines, U251 and Gl261. An invasive pattern being a GB hallmark, our data suggests that the DOTA-C6-anti-integrin peptide may aid in developing a GB theranostic agent.</div></div><div><h3>A","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103761"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828553","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":"EFEITO DO SILENCIAMENTO DA CHAPERONA ERP29 NA EXPRESSÃO DE GENES DA VIA PI3K/AKT EM CÉLULAS DE CÂNCER DE FARINGE SENSÍVEIS E RESISTENTES À CISPLATINA","authors":"Rodrigo Costa Cespedes, Juliana Carron, Carmen Silvia Passos Lima, Gustavo Jacob Lourenço","doi":"10.1016/j.htct.2025.103780","DOIUrl":"10.1016/j.htct.2025.103780","url":null,"abstract":"<div><h3>Introdução/Justificativa</h3><div>As proteínas chaperonas, como a ERp29, são essenciais para o enovelamento e para a secreção de proteínas do retículo endoplasmático para o complexo de Golgi. Alterações nesse processo podem comprometer a funcionalidade proteica e influenciar o comportamento celular, incluindo a progressão tumoral. O silenciamento do gene ERP29 foi associado ao aumento da progressão de células tumorais da faringe, sugerindo que a ERp29 pode atuar na inibição de fenótipos tumorais agressivos. No entanto, os mecanismos envolvidos nessa regulação ainda não estão esclarecidos. A via PI3K/AKT desempenha um papel importante na progressão tumoral, regulando processos como sobrevivência celular e resposta inflamatória no microambiente tumoral. No entanto, a relação entre ERP29 e a modulação dessa via ainda não foi elucidada.</div></div><div><h3>Objetivos</h3><div>O objetivo deste trabalho foi avaliar os padrões de expressão de genes da via PI3K/AKT na linhagem de células tumorais de faringe FaDu, com supressão do gene ERP29, em três condições experimentais: FaDu, FaDu tratada com cisplatina (CDDP) (FaDu-CDDP) e FaDu resistente à CDDP (FaDu-R).</div></div><div><h3>Materiais e Métodos</h3><div>A linhagem celular FaDu (HTB-43, ATCC) é sensível à CDDP e foi cultivada seguindo protocolo padrão. A resistência celular foi induzida com 0,5 µM de CDDP, conforme protocolo previamente estabelecido. O gene ERP29 foi silenciado utilizando RNA de interferência (s21576, Invitrogen). Para identificar genes da via PI3K/AKT modulados pelo ERP29, o cDNA de cada amostra foi amplificado utilizando a placa TaqMan Array Human Molecular Mechanisms of Cancer (4418806, Applied Biosystems). Os resultados foram validados por qPCR. O teste t foi utilizado para comparação entre os grupos e os resultados foram expressos como fold change (FC). O valor de p < 0,05 foi considerado significativo.</div></div><div><h3>Resultados</h3><div>A expressão do gene SRC foi maior nas células FaDu-CDDP em comparação com FaDu (FC: 3,4, p = 0,02) e FaDu-R (FC: 4,6, p < 0,001). No entanto, após o silenciamento de ERP29, os níveis de SRC tornaram-se semelhantes entre as linhagens celulares. O gene AKT1 apresentou maior expressão nas células FaDu (FC: 4,2, p = 0,03) e FaDu-CDDP (FC: 3,9, p = 0,04) em comparação com FaDu-R. No entanto, nas células com ERP29 silenciado, a expressão de AKT1 foi maior em FaDu do que em FaDu-CDDP (FC: 1,7, p = 0,04). Não foram observadas diferenças significativas na expressão de ITGAV entre as linhagens celulares. Entretanto, após o silenciamento do ERP29, ITGAV apresentou maior expressão em FaDu (FC: 3,3, p = 0,02) e FaDu-R (FC: 2,3, p = 0,01) em comparação com FaDu-CDDP. A expressão de JUN foi maior em FaDu-CDDP em relação a FaDu-R (FC: 2,6, p = 0,04). Entretanto, após o silenciamento do ERP29, a expressão de JUN foi maior em FaDu em comparação com as outras linhagens celulares (FC: 4,5, p= 0,03 e FC: 3,0, p= 0,03). A expressão de MDM2 foi meno","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103780"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828173","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":"PSMA PET/CT FOR DETECTING BRAIN METASTASIS IN ESOPHAGEAL CANCER: A CASE REPORT","authors":"FABÍOLA FURTUOSO ZARPELÃO ,&nbsp;Renata Erbert CONTRICIANI ,&nbsp;Caroline TORRICELLI-CORRÊA ,&nbsp;Natália TOBAR ,&nbsp;Larissa Ariel Oliveira CARRILHO ,&nbsp;Leo Victor KIM ,&nbsp;Luiz Roberto LOPES ,&nbsp;Nelson Adami ANDREOLLO ,&nbsp;Maria Carolina Santos MENDES ,&nbsp;Elba Cristina Sá de Camargo ETCHEBEHERE ,&nbsp;José Barreto Campello CARVALHEIRA","doi":"10.1016/j.htct.2025.103813","DOIUrl":"10.1016/j.htct.2025.103813","url":null,"abstract":"<div><h3>Introduction/Justification</h3><div>PET/CT with prostate-specific membrane antigen (PSMA) has been investigated in various scenarios beyond prostate cancer, with PSMA expression reported in multiple solid tumor tissues, including their neovascular endothelium.[1] We present the case of a patient with esophageal cancer who developed brain metastasis, emphasizing the critical role of 18 F-PSMA PET/CT imaging in detecting metastatic lesions and its potential impact on guiding treatment strategies.</div></div><div><h3>Report</h3><div>G. H. B., a 71-year-old Brazilian male with a history of smoking, alcohol consumption and gastroesophageal reflux disease, was diagnosed with esophagogastric adenocarcinoma in 2024. 18 F-FDG PET/CT staging revealed a localized neoplasm at the esophagogastric junction (6.4 cm, SUV=15.1) and regional paratracheal lymphadenopathy (SUV = 17.2), with no evidence of distant metastasis. The patient initiated neoadjuvant chemotherapy with the FLOT regimen (fluorouracil, leucovorin, oxaliplatin, and docetaxel) and after four cycles, he underwent 18 F-FDG and 18 F-PSMA PET/CT. 18 F-FDG PET/CT revealed disease progression with increased primary lesion metabolic activity, new paratracheal lymphadenopathy and a right temporal lobe lesion consistent with metastasis. In comparison, 18 F-PSMA PET/CT showed higher 18 F-PSMA uptake in the temporal lobe lesion, similar uptake in the distal esophagus, and reduced uptake in the mediastinal lymph nodes. The multidisciplinar team contraindicated esophagectomy, recommending radiotherapy for the central nervous system metastasis over neurosurgery, and palliative systemic treatment.</div></div><div><h3>Conclusion</h3><div>To our knowledge, this is the first reported case of brain metastasis from esophageal cancer identified using 18 F-PSMA PET/CT. The increased 18 F-PSMA uptake in the brain lesion, compared to 18 F-FDG PET/CT, may be attributed to PSMA overexpression in the neovascular endothelium of non-prostate cancers.[2] 18 F-PSMA PET/CT represents a novel diagnostic tool for non-prostate cancers, potentially offering higher sensitivity for detecting brain metastases than 18 F-FDG PET/CT. Further clinical trials are warranted to investigate its role in gastrointestinal malignancies.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103813"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828176","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":"AUTOIMMUNE ENCEPHALITIS AND PARANEOPLASTIC SYNDROMES: A CLINICAL AND FDG-PET/CT STUDY","authors":"Maurício Martins Baldissin ,&nbsp;Edna Marina de Souza ,&nbsp;Nancy Watanabe ,&nbsp;Elba Cristina Sá de Camargo Etchebehere ,&nbsp;Fernando Cendes ,&nbsp;Bárbara Juarez Amorim","doi":"10.1016/j.htct.2025.103791","DOIUrl":"10.1016/j.htct.2025.103791","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction/Justification&lt;/h3&gt;&lt;div&gt;Autoimmune encephalitis (AE) is a debilitating neurological disorder characterized by inflammation of brain tissue. Frequently, it is associated with the detection of highly specific antibodies, as such as NMDA, Yo, GAD, Hu, among others. Oftentimes, this condition is expressed as a paraneoplastic syndrome (PNS), for which the neurological manifestation precedes the tumor diagnosis up to 4 years in about two-thirds of the patients.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;This work applied the review of clinical findings and FDG-PET/CT images analysis to characterize and explore the outcomes of patients diagnosed with AE, both clinically and by antibodies test.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and Methods&lt;/h3&gt;&lt;div&gt;The study includes 37 patients, aged from 13 to 75 (47.08 ± 20,00 years), 65% female, who had been presented neurological manifestations of encephalitis and PNS. The group of patients was divided according to the antibodies detected (NMDA, Yo, Hu, LGI1, GAD, Amphiphysin, Aquaporin-4), being also studied a group of patients with negative antibodies and untested. Retrospectively, the clinical records were analyzed by the neurology staff, being the clinical manifestations and the results of antibodies tests correlated with FDG-PET/CT brain images, analyzed by an expert in nuclear medicine.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Among the groups studied, 24.3% had suspicion or confirmed neoplasia (most of them breast or thyroid lesions), being 49% of the patients positive for antibodies related autoimmune encephalitis (AE). In the pretreatment phase, patients with Yo antibodies, manifested epilepsy and cerebellar ataxia, with FDG-PET/CT revealing hypermetabolism in the basal ganglia, cingulate gyri, thalamus, and midbrain, with hypometabolism in the cerebellar hemispheres. Hu antibodies has been associated with epilepsy, sensitive and behavior alterations, being the hypermetabolism in the cingulate gyrus and hypometabolism in the cerebellar hemispheres identified in the PET/CT images; on the other side, GAD antibodies resulted in higher FDG uptake in the thalamus and midbrain, with hypometabolism in the frontal lobes. In this case, the neurological manifestations include epilepsy, ataxia with aspects of stiff-person syndrome, behavior and sensitive alterations. Most of the clinical manifestations mentioned has also been observed in patients with NMDA antibodies, who expressed cingulate gyri, precuneus, parietal lobes and basal ganglia hypermetabolism, and cingulate hypermetabolism, with cerebellar hemispheres hypometabolism, characterizing an anteroposterior gradient of FDG uptake. LGI1 antibodies resulted in hypermetabolism in the basal ganglia and temporal mesial lobe, with frontal hypometabolism. For most of the groups of patients, epilepsy was a common manifestation, followed by behavior and sensitive alterations. The exception is the aquaporin-4 antibody for which muscular disorders are the main s","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103791"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828348","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":"BRAIN-TO-LIVER RATIO FROM 18F-FDG-PET/CT AS A PROGNOSTIC MARKER IN MULTIPLE MYELOMA","authors":"Tiago Pessolo Dos Santos ,&nbsp;Maria Emília Seren Takahashi ,&nbsp;Christopher Cralcev ,&nbsp;Eliana Miranda ,&nbsp;Marcos Paulo DS Silva ,&nbsp;Felipe Cardoso de Souza ,&nbsp;Carmino de Souza ,&nbsp;Celso Dario Ramos","doi":"10.1016/j.htct.2025.103793","DOIUrl":"10.1016/j.htct.2025.103793","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction/Justification&lt;/h3&gt;&lt;div&gt;18F-FDG PET/CT imaging is widely used in oncology for staging and monitoring treatment response in multiple myeloma (MM). Studies have shown reduced 18F-FDG uptake in the brains of patients with disseminated malignancies, such as malignant lymphoma and other aggressive cancers. This phenomenon is likely associated with the Warburg effect and hyperlactatemia.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;This study aimed to evaluate whether the brain-to-liver ratio (BLR) of 18F-FDG uptake in MM patients serves as a prognostic marker.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and Methods&lt;/h3&gt;&lt;div&gt;A total of 82 MM patients diagnosed between March 2011 and May 2019 were included, with a median follow-up of 25 months (range: 0.1–113). All patients underwent whole-body 18F-FDG PET/CT at diagnosis after fasting for at least six hours and with peripheral blood glucose levels below 180 mg/dL. A dose of 0.1 mCi/kg of 18F-FDG was intravenously administered 60 minutes before image acquisition. Brain and liver standardized uptake values (SUVmean) were determined using automated whole-brain segmentation and a spherical volume of interest (VOI) in the liver. The BLR was calculated by dividing the brain SUVmean by the liver SUVmean for each patient. Descriptive and bivariate analyses were performed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared with the log-rank test (IBM-SPSS v.24). The follow-up data were updated in January 2025.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The cohort included 55% male patients, with a median age of 64 years (range: 39–87). At diagnosis, 67% had ISS stage III disease, 16% had an ECOG performance status ≥ 2, and 88% presented with bone lesions. Chemotherapy was administered to 94% of patients, with 27% receiving bortezomib. A complete response (CR), very good partial response (VGPR), or partial response (PR) was achieved by 71% of patients. Disease progression occurred in 47% of cases, and the overall mortality rate was 69%. The 60-month OS and PFS rates were 35% and 10%, respectively. The BLR was significantly correlated with sex (R= 32%, P= 0.006), overweight status (R = 32%, P =0.007), ISS stage (R = 23%, P = 0.04), and beta-2 microglobulin levels (R = 42%, P &lt; 0.0001). Patients with a median BLR &gt;2.7 had significantly better OS (50% vs. 13%, P= 0.006) and PFS (3% vs. 0%, P = 0.006).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;BLR derived from 18F-FDG-PET/CT at diagnosis appears to be a strong prognostic indicator of OS and PFS in MM patients, with a cut-off value of 2.7. BLR also correlates with beta-2 microglobulin, a well-established serum marker of tumor burden, and ISS stage III disease. The lower 18F-FDG uptake in more aggressive MM cases may be associated with neoplastic lactate production. Given that brain cells can utilize lactate as an alternative energy source when blood lactate levels rise, this may result in reduced brain ","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103793"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828350","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":"QUANTIFYING INTERSPECIFIC COMPETITION BETWEEN CANCER AND NORMAL CELLS USING USING NONLINEAR MIXED EFFECTS AND ORDINARY DIFFERENTIAL EQUATION MODELING","authors":"Letícia Fernanda Alves ,&nbsp;Mauro César Cafundó Morais ,&nbsp;João Frederico Costa Azevedo Meyer ,&nbsp;Diego Samuel Rodrigues","doi":"10.1016/j.htct.2025.103779","DOIUrl":"10.1016/j.htct.2025.103779","url":null,"abstract":"<div><h3>Introduction/Justification</h3><div>Tumor growth has been widely studied through various methodologies. In mathematical oncology, researchers use ordinary differential equations (ODEs) to analyze tumor dynamics. These models present meaningful parameters to link mathematical theory with experimental data. For in vitro cocultures, parameters quantifying cellular competition clarify interactions between tumor and normal cells.</div></div><div><h3>Objectives</h3><div>This research investigates the interaction between cancer and normal cells during competition, focusing on the in vitro growth of SK-MEL-147 (metastatic melanoma) and HaCaT (immortalized epithelial cells) cell lines. Using an ODE model with cell numbers as dependent variables, we quantify interspecific competition through the parameters α_{12} (impact of SK-MEL-147 on HaCaT) and α_{21} (impact of HaCaT on SK-MEL-147).</div></div><div><h3>Materials and Methods</h3><div>The in vitro cell growth experiments from Morais textit{et al}., (2017), https://doi.org/10.1038/s41598-017-07553-6, allowed us to estimate parameters for Gatenby's 1996 ODE model. We used a nonlinear mixed effects model from NLMEModeling (https://doi.org/10.48550/arXiv.2011.06879) to account for observation errors and biological variability.</div></div><div><h3>Results</h3><div>The curve fitting matched the experimental data for both cell types. Parameter estimates showed that SK-MEL-147 cells experienced stronger inhibition from HaCaT cells than the reverse, suggesting normal cells hinder cancer cell growth upon contact.</div></div><div><h3>Conclusion</h3><div>Nonlinear mixed effects modeling successfully fit Gatenby's mathematical model to the experimental data, providing competition parameters that clarified interspecific interactions in tumor dynamics. Such models can predict cell growth behavior, supporting experimental design and reducing the need for preliminary textit{in vitro} tests.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103779"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828172","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":"THE ROLE OF PSMA PET/CT IN THE CHARACTERIZATION OF HEAD AND NECK SQUAMOUS CELL CARCINOMA","authors":"Hadila da Silva Veras Sousa,&nbsp;Victor Cabral Costa Ribeiro Heringer,&nbsp;Ligia Traldi Macedo,&nbsp;Najua Abou Arab,&nbsp;Simone Kuba,&nbsp;Celso Dario Ramos,&nbsp;Carmen Silvia Passos Lima","doi":"10.1016/j.htct.2025.103784","DOIUrl":"10.1016/j.htct.2025.103784","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction/Justification&lt;/h3&gt;&lt;div&gt;Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy, often diagnosed at advanced stages. The 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) reflects glycolytic activity in tissues and has been widely used for staging and monitoring HNSCC. However, its specificity is limited by false positives in inflammatory processes. PET/CT with prostate-specific membrane antigen (PSMA) has been investigated as an alternative to 18F-FDG due to its expression in tumor neovasculature, but its role in HNSCC remains unclear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;To evaluate the uptake patterns of 18F-PSMA-1007 PET/CT in HNSCC, in comparison with 18F-FDG PET/CT, aiming to explore its potential in tumor characterization, staging, and monitoring.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and Methods&lt;/h3&gt;&lt;div&gt;Patients with advanced locoregional HNSCC, either at initial diagnosis or with tumor relapses, were enrolled in the study. Individuals who had undergone surgical tumor resection or received chemotherapy and/or radiotherapy within the last six months were excluded. All enrolled patients underwent 18F-FDG PET/CT and 18F-PSMA-1007 PET/CT imaging, with a 24-hour interval between the exams. The images were analyzed independently by two nuclear medicine physicians and one radiologist. Statistical comparisons between groups were performed using the t-test, with significance set at P &lt; 0.05.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Fourteen patients (nine at initial diagnosis, five with recurrent disease) were analyzed using both PET/CT imaging modalities. The median age was 61 years (range: 49-81), with eleven males and three females. Most patients were current or former smokers and alcohol consumers, had good performance status (ECOG 0), and presented with stage IV tumors. The primary tumors were located in the oropharynx, larynx, and oral cavity, with one sinonasal tumor. Recurrences, were observed in locoregional lymph nodes, lungs, and bones. HNSCC lesions were typically characterized by FDG uptake, although most lesions also exhibited varying degrees of PSMA uptake. In primary tumors and nodal disease, the mean ± SD and median (range) SUV values obtained with FDG PET/CT at 1 hour were 25.6 ± 16.4 and 21.0 (10.7–59.8), and 11.7 ± 7.7 and 8.6 (2.7-26.4), respectively. For PSMA PET/CT, the mean ± SD and median (range) SUV values at 1 hour in primary tumors and nodal disease were 4.5 ± 1.3 and 4.3 (2.9-6.3), and 4.9 ± 2.6 and 3.9 (2.8-10.2), respectively. FDG uptake values were higher than PSMA uptake values in primary tumors (P &lt; 0.001) and lymph nodes (P = 0.01).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;HNSCC lesions were more effectively detected by FDG PET/CT, highlighting its superior sensitivity for assessing tumor activity. However, PSMA uptake in most tumors suggests the coexistence of glycolytic activity and neoangiogenesis, reinforcing the value of integrating FD","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103784"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828824","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":"COMPARATIVE RADIOLABELING OF THE CYCLIC PEPTIDE CTHRSSVVC WITH [68GA]GALLIUM AND [18F]FLUORINE. A POTENTIAL PROBE FOR MOLECULAR IMAGING OF CD163⁺ MACROPHAGES","authors":"Carlos Alberto Rossatto-Jr ,&nbsp;Rosemeire Aparecida Silva ,&nbsp;Fabio Luiz Navarro Marques","doi":"10.1016/j.htct.2025.103806","DOIUrl":"10.1016/j.htct.2025.103806","url":null,"abstract":"<div><h3>Introduction/Justification</h3><div>CD163⁺ macrophages play a critical role in chronic inflammation, cancer, and hematologic disorders, making them a promising target for molecular imaging. These cells contribute to tumor immunosuppression, disease progression, and poor prognosis in solid and hematologic tumors. Recent studies indicate that CD163 is a relevant biomarker in Hodgkin's lymphoma, multiple myeloma, and leukemias, which are directly associated with tumor resistance and immune evasion. The cyclic peptide CTHRSSVVC has been identified as a CD163 ligand, showing high reactivity with inflammatory and atherosclerotic lesions, suggesting its potential for targeting CD163⁺ macrophages. In vitro assays demonstrated that [111In]In-DOTA-CTHRSSVVC binds to atherosclerotic plaques, further supporting its applicability in molecular imaging of inflammation and cancer. Cyclic peptides are widely used in radiotracer development due to their high specificity, enzymatic stability, and resistance to degradation. Radiolabeling of these peptides with PET radioisotopes such as 68Ga3+ and [¹⁸F]AlF2+ expands their potential applications in tracking inflammatory processes and hematologic malignancies.</div></div><div><h3>Objectives</h3><div>To evaluate the radiolabeling efficiency and chemical stability of the NOTA-CTHRSSVVC cyclic peptide with 68Ga3+ and [18F]AlF2+, aiming to develop a novel radiopharmaceutical for molecular imaging of CD163⁺ macrophages.</div></div><div><h3>Materials and Methods</h3><div>The NOTA-CTHRSSVVC conjugate was radiolabeled [68Ga]Ga(AcO)3 or [18F]AlF2+, which were prepared in 0.2 M sodium acetate buffer (pH 4.1); reactions carried out under different peptide amounts. When necessary, the final products were purified using solid phase columns. The radiochemical efficiency was assessed by HPLC coupled with a gamma radiation detector, while chemical stability was evaluated in the labeling solution for up to 4 hours. The partition coefficient (logP) was determined in n-octanol/water system, in triplicate.</div></div><div><h3>Results</h3><div>The NOTA-CTHRSSVVC peptide was successfully radiolabeled and purified with the [68Ga]Ga-NOTA-CTHRSSVVC exhibited a radiochemical purity of 97.8% (n = 3), while [18F]AlF-NOTA-CTHRSSVVC reached 95.5% (n = 3). Both radiolabeled peptides demonstrated high chemical stability, maintaining their integrity for up to 4 hours in physiological solution. The logP analysis indicated a hydrophilic profile with the value of -3.08 ± 0.16.</div></div><div><h3>Conclusion</h3><div>The radiolabeling of the NOTA-CTHRSSVVC peptide with 68Ga3+ and [18F]AlF2+ was efficient and stable, demonstrating chemical feasibility for the development of a novel radiopharmaceutical. Given the potential interaction of the peptide with CD163, future investigations may focus on assessing its biological affinity and molecular imaging applications for CD163⁺ macrophages in hematologic and inflammatory diseases.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103806"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829768","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":"EVALUATION OF THE AFFINITY OF RADIOLABELED PEPTIDE [¹³¹I]I-DEDEYFELV FOR EGFR-OVEREXPRESSING RECEPTORS IN ADULT-TYPE DIFFUSE GLIOMAS","authors":"Julia Calviello Giordano ,&nbsp;Fernanda Paiva Augusto Rodrigues ,&nbsp;Danielle Vieira Sobral ,&nbsp;Leonardo Lima Fuscaldi ,&nbsp;Fabio Luiz Navarro Marques ,&nbsp;Marycel Figols de Barboza ,&nbsp;João Luiz vitorino Araújo ,&nbsp;Luciana Malavolta","doi":"10.1016/j.htct.2025.103787","DOIUrl":"10.1016/j.htct.2025.103787","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction/Justification&lt;/h3&gt;&lt;div&gt;Cancer remains one of the leading causes of death worldwide. Among the various tumor sites, the central nervous system is particularly significant, with gliomas accounting for the majority of primary brain tumors. In gliomas, alterations in the tyrosine kinase pathway lead to the overexpression of the Epidermal Growth Factor receptor (EGFr). Over the past decades, radiolabeled peptides with high affinity for EGFr have emerged as promising molecular targets with potential applications in both diagnosis and therapy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;This study aimed to evaluate the affinity of the peptide DEDEYFELV, radiolabeled with iodine-131 (¹³¹I), for EGFr-overexpressing receptors in adult-type diffuse gliomas using tumor tissue samples.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and Methods&lt;/h3&gt;&lt;div&gt;The peptide was synthesized using solid-phase peptide synthesis following the Fmoc/tBu strategy. Upon completion of the synthesis, the peptide was characterized and purified via high-performance liquid chromatography (HPLC). DEDEYFELV (20 nmol) was radiolabeled with [¹³¹I]NaI (18.5 MBq) using the chloramine-T method. The radiochemical yield of [¹³¹I]I-DEDEYFELV was determined via chromatography on Whatman 3MM strips using a 95% MeOH / 5% H₂O eluent. Binding studies of [¹³¹I]I-DEDEYFELV with neoplastic tissue homogenates were conducted at 1 and 4 h of incubation and quantified using an automatic gamma counter. Tumor tissue homogenates were obtained from surgical resections performed by a designated neurosurgeon, following informed consent. Gliomas were confirmed through pathological analysis, and tumor samples were preserved at -80°C. All human protocols adhered to local ethical guidelines (Protocol number CEP – FCMSCSP: CAAE 79336124.7.0000.5479). Statistical analysis was conducted using ANOVA or Student's t-test.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The peptide DEDEYFELV was successfully synthesized with a yield of approximately 92%. Mass spectrometry and HPLC analyses confirmed efficient synthesis, cleavage, and purification, as evidenced by a single peak and a molecular mass corresponding to the expected peptide. Radiolabeling was achieved with a radiochemical yield exceeding 95%. Binding studies of [¹³¹I]I-DEDEYFELV with neoplastic tissue homogenates showed values of 3.25 ± 0.31% for high-grade tumors, 2.62 ± 0.34% for low-grade tumors, and 1.61 ± 0.25% for tumors of unknown grade at 1 h of incubation (n = 5). At 4 h, the binding values increased to 6.45 ± 0.66% for high-grade tumors, 10.27 ± 1.58% for low-grade tumors, and 7.74 ± 1.21% for tumors of unknown grade (n = 5).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;These findings demonstrate that the radiolabeled peptide [¹³¹I]I-DEDEYFELV exhibits specific binding to EGFr-overexpressing tumor tissues, with an increasing affinity over time. The higher binding observed at 4 h suggests favorable interaction dynamics, particularly in low-grade gliomas. These resu","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103787"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828452","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":"PREPARATION OF 1-[18F]FLUORO-2-IODOETHANE AS A PROSTHETIC GROUP FOR [18F]FLUOROETILATION","authors":"Marcelle Vitória Carreira Dos Santos ,&nbsp;Gabriela Viana de Souza ,&nbsp;Helio Alexandre Stefani ,&nbsp;Fabio Luiz Navarro Marques","doi":"10.1016/j.htct.2025.103797","DOIUrl":"10.1016/j.htct.2025.103797","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction/Justification&lt;/h3&gt;&lt;div&gt;[18F]Fluorine is of considerable importance in radiochemistry for positron emission tomography (PET) due to its decay characteristics (18F; beta+ 96.7%, T1 = 2. 109:8 min). Numerous methods for introducing 18F into organic molecules have been developed, with alkylation being one of the methods. Thus, developing the radiochemistry process for the fluorination of dihaloalkyl compounds is a crucial step for the development of new radiotracers.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;This work aims to prepare the 1-[18F]fluoro-2-iodo-ethane as a prosthetic group for radiolabeling amine or alcohol functionalized molecules, focusing on developing the radiotracers for molecular imaging.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and Methods&lt;/h3&gt;&lt;div&gt;[18F]Fluoride was produced by the 18O(p,n)18F reaction on [18O]water using cyclotron (GE 16.5 MeV). Radiolabeling method 1: [18F]Fluoride was trapped in a QMA cartridge and released by eluting tetraethylammonium bicarbonate (TEAHCO3 (7.5 mg, 2.47 μmol) in methanol into a vial. The methanol solution was heated at 100oC with a gentle stream of N2 until methanol was evaporated. Acetonitrile (AcN) was added (0.5 mL × 2) and evaporated to complete drying the system. A solution containing 9 mg (3.19 μmol) of 1,2-diiodoethane in 0.5 mL AcN was added and heated at 100oC for 10 or 15 min. Radiolabeling method 2: Water solution containing [18F]fluoride was added to a vial and dried by azeotropic evaporation with acetonitrile (0.5 mL × 2) at 100 oC with a gentle stream of N2 over 10 min. An acetonitrile solution containing TEAHCO3 (7.5 mg, 2.47 μmol) or TBAHSO4 (8.3 mg, 2.47 μmol) was added and evaporated; finally, 9 mg (3.19 μmol) of 1,2-diiodoethane in 0.5 mL of AcN was added and heated at 100oC for 10 min. At the end of the reactions, vials were allowed to reach room temperature; a sample was removed and analyzed in TLC-SG and TLC-RPc18 using ethyl acetate or ethanol as the mobile phase. [18F]fluoride ion and [18F]fluoride/ammonium quaternary ion pair were also analyzed by TLC chromatography. Stripes were cut in segments of 1 cm and read in a well counter.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;All the chromatographic systems evaluated presented [18F]fluoride and [18F]fluoride/ammonium quaternary retained in the origin of the systems. Samples of the reaction showed a radioactive product moving to the front of the TLC-RPc18 using ethanol, and this TLC system was used to analyze the reaction efficiency. Radiochemical yield was calculated considering the Rf 0.5-1.0 radioactive counts in the TLC-RPc18/EtOH. Reaction under condition 1: heating time: 10 min = 24.5%, 15 min = 10.6%. Reaction under condition 2: TEAHCO3 - 10 min = 47.6%, TBAHSO4 - 10 min = 24.8%.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The results demonstrated the feasibility to produce 1-[18F]fluoro-2-iodo-ethane by both techniques, and heating time and kind of ammonium salt can influence the reaction yield. Directly adding [18","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 103797"},"PeriodicalIF":1.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828322","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}