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1.
Bioorg Med Chem ; 33: 115996, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33494011

RESUMO

In the present work, the radioimmunoconjugates 111In-DTPA-trastuzumab and 177Lu-DOTA-trastuzumab were evaluated regarding the influence of the chelating agents on the physical-chemical parameters and human epidermal growth factor receptor 2 (HER2) tumor cell binding. Data showed that both chelating agents, at predetermined molar ratios (antibody:chelator - 1:10 and 1:20), did not influence the immunoconjugates integrity, the radiolabeling process and the radiolabeled antibodies stability. However, differences were observed in the lipophilic feature between DOTA and DTPA radioimmunoconjugates and in the specific binding to SK-BR-3 tumor cells (HER2 positive). Therefore, this study showed the importance of assessing the influence of chelating agents and their molar ratios in the development process of radioimmunoconjugates.


Assuntos
Anticorpos Monoclonais/farmacologia , Quelantes/farmacologia , Imunoconjugados/farmacologia , Receptor ErbB-2/antagonistas & inibidores , Anticorpos Monoclonais/química , Quelantes/síntese química , Quelantes/química , Relação Dose-Resposta a Droga , Humanos , Imunoconjugados/química , Estrutura Molecular , Receptor ErbB-2/metabolismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
2.
Nanotheranostics ; 8(1): 112-126, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164500

RESUMO

Background: Nanotechnology has revolutionized medicine, especially in oncological treatments. Gold nanoparticles (AuNPs) stand out as an innovative alternative due to their biocompatibility, potential for surface modification, and effectiveness in radiotherapeutic techniques. Given that prostate cancer ranks as one of the leading malignancies among men, there's a pressing need to investigate new therapeutic approaches. Methods: AuNPs coated with bovine serum albumin (BSA) were synthesized and their cytotoxicity was assessed against prostate tumor cell lines (LNCaP and PC-3), healthy prostate cells (RWPE-1), and endothelial control cells (HUVEC) using the MTS/PMS assay. For in vivo studies, BALB/C Nude mice were employed to gauge the therapeutic efficacy, biodistribution, and hematological implications post-treatment with BSA-coated AuNPs. Results: The BSA-coated AuNPs exhibited cytotoxic potential against PC-3 and LNCaP lines, while interactions with RWPE-1 and HUVEC remain subjects for further scrutiny. Within animal models, a diverse therapeutic response was observed, with certain instances indicating complete tumor regression. Biodistribution data emphasized the nanoparticles' affinity towards particular organs, and the majority of hematological indicators aligned with normative standards. Conclusions: BSA-coated AuNPs manifest substantial promise as therapeutic tools in treating prostate cancer. The present research not only accentuates the nanoparticles' efficacy but also stresses the imperative of optimization to ascertain both selectivity and safety. Such findings illuminate a promising trajectory for avant-garde therapeutic modalities, holding substantial implications for public health advancements.


Assuntos
Nanopartículas Metálicas , Neoplasias da Próstata , Masculino , Animais , Camundongos , Humanos , Ouro/farmacologia , Próstata/metabolismo , Soroalbumina Bovina/metabolismo , Distribuição Tecidual , Camundongos Nus , Nanopartículas Metálicas/uso terapêutico , Camundongos Endogâmicos BALB C , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/metabolismo , Radioisótopos
3.
Appl Biochem Biotechnol ; 185(4): 863-874, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29362989

RESUMO

Early and accurate detection of primary or metastatic tumors is of great value in staging, treatment management, and prognosis. Tumor angiogenesis plays an essential role in the growth, invasion, and metastatic spread of solid cancers, and so, is a promising approach for tumor imaging. The GX1 (CGNSNPKSC) peptide was identified by phage display library and has been investigated as a marker for human cancers. This study aims to evaluate the 99mTc-HYNIC-PEG4-c (GX1) as a biomarker for tumor imaging. Our results showed that GX1 specifically binds to tumor cells in vitro. SKMEL28 and MDA-MB231 cells achieved total binding peak at 60 min of incubation. For B16F10 and MKN45 cells, the total and specific binding were similar during all time points, while A549 cell line showed rapid cellular total uptake of the tracer at 30 min of incubation. Biodistribution showed low non-specific uptakes and rapid renal excretion. Melanoma tumors showed enhanced GX1 uptake in animal model at 60 min, and it was significantly blocked by cold peptide. The radiotracer showed tumor specificity, especially in melanomas that are highly vascularized tumors. In this sense, it should be considered in future studies, aiming to evaluate degree of angiogenesis, progression, and invasion of tumors.


Assuntos
Marcação por Isótopo , Melanoma/diagnóstico por imagem , Neoplasias Experimentais/diagnóstico por imagem , Neovascularização Patológica/diagnóstico por imagem , Peptídeos , Compostos Radiofarmacêuticos , Células A549 , Animais , Humanos , Melanoma/metabolismo , Camundongos , Neoplasias Experimentais/metabolismo , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Peptídeos/química , Peptídeos/farmacocinética , Peptídeos/farmacologia , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/farmacologia
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