Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
Eur J Nucl Med Mol Imaging ; 51(2): 395-404, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37796306

RESUMO

PURPOSE: A reliable method for regional in vivo imaging of radiation-induced cellular damage would be of great importance for the detection of therapy-induced injury to healthy tissue and the choice of adequate treatment of radiation emergency patients in both civilian and military events. This study aimed to investigate in a mouse model if positron emission tomography (PET) imaging with proliferation and apoptosis markers is potentially suitable for this purpose. METHODS: Four groups, including twenty mice (wild-type C57BL/6) each, were whole-body irradiated with 0 Gy, 0.5 Gy, 1 Gy, and 3 Gy and examined by PET over a six-month period at defined time points. 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) and 2-(5-[18F]fluoropentyl)-2-methyl malonic acid ([18F]ML-10) were used to visualise proliferation and apoptosis. Regional standard uptake values were compared with respect to irradiation dose over time. Histologic data and peripheral blood cell values were correlated with the PET results. RESULTS: The hematopoietic bone marrow showed a significantly increased [18F]FLT signal at early time points after radiation exposure (day 3 and day 7). This correlated with blood parameters, especially leukocytes, and histological data. A significantly increased [18F]FLT signal also occurred in the gastrointestinal tract and thymus at early time points. An increased [18F]ML-10 signal related to irradiation doses was observed in the bone marrow on day 8, but there was a high variability of standard uptake values and no correlation with histological data. CONCLUSION: [18F]FLT showed potential to visualise the extent, regional distribution and recovery from radiation-induced cellular damage in the bone marrow, gastrointestinal tract and thymus. The potential of [18F]FLT imaging to assess the extent of bone marrow affected by irradiation might be especially useful to predict the subsequent severity of hematopoietic impairment and to adapt the therapy of the bone marrow reserve. [18F]ML-10 PET proved to be not sensitive enough for the reliable detection of radiation induced apoptosis.


Assuntos
Tomografia por Emissão de Pósitrons , Irradiação Corporal Total , Humanos , Camundongos , Animais , Irradiação Corporal Total/efeitos adversos , Camundongos Endogâmicos C57BL , Tomografia por Emissão de Pósitrons/métodos , Modelos Animais de Doenças , Proliferação de Células/efeitos da radiação , Apoptose , Didesoxinucleosídeos
2.
Bioorg Med Chem Lett ; 48: 128241, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34217827

RESUMO

Receptor-specific peptides labeled with positron emitters play an important role in the clinical imaging of several malignancies by positron emission tomography (PET). Radiolabeled heterobivalent bispecific peptidic ligands (HBPLs) can target more than one receptor type and by this - besides exhibiting other advantages - increase tumor imaging sensitivity. In the present study, we show the initial in vivo evaluation of the most potent heterobivalent gastrin-releasing peptide receptor (GRPR)- and vasoactive intestinal peptide receptor subtype 1 (VPAC1R)-bispecific radiotracer and determined its tumor visualization potential via PET/CT imaging. For this purpose, the most potent described HBPL was synthesized together with its partly scrambled heterobivalent monospecific homologs and its monovalent counterparts. The agents were efficiently labeled with 68Ga3+ and evaluated in an initial PET/CT tumor imaging study in a human prostate carcinoma (PCa) xenograft rat tumor model established for this purpose. None of the three 68Ga-HBPLs enabled a clear tumor visualization and a considerably higher involvement in receptor-mediated uptake was found for the GRPR-binding part of the molecule than for the VPAC1R-binding one. Of the monovalent radiotracers, only [68Ga]Ga-NODA-GA-PESIN could efficiently delineate the tumor, confirming the results. Thus, this work sets the direction for future developments in the field of GRPR- and VPAC1R-bispecific radioligands, which should be based on other VPAC1R-specific peptides than PACAP-27.


Assuntos
Peptídeos/química , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata/diagnóstico por imagem , Receptores da Bombesina/química , Receptores Tipo I de Polipeptídeo Intestinal Vasoativo/química , Humanos , Masculino , Estrutura Molecular
3.
ChemMedChem ; 13(12): 1230-1237, 2018 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-29667369

RESUMO

64 Cu is a cyclotron-produced radionuclide which offers, thanks to its characteristic decay scheme, the possibility of combining positron emission tomography (PET) investigations with radiotherapy. We evaluated the Alceo system from Comecer SpA to automatically produce 64 Cu for radiolabelling purposes. We established a 64 Cu production routine with high yields and radionuclide purity in combination with excellent operator radiation protection. The carbonic anhydrase XII targeting 6A10 antibody Fab fragment was successfully radiolabelled with the produced 64 Cu, and proof-of-principle small-animal PET experiments on mice bearing glioma xenografts were performed. We obtained a high tumor-to-contralateral muscle ratio, which encourages further in vivo investigations of the radioconjugate regarding a possible application in diagnostic tumor imaging.


Assuntos
Anidrases Carbônicas/imunologia , Radioisótopos de Cobre/química , Fragmentos Fab das Imunoglobulinas/imunologia , Neoplasias/diagnóstico por imagem , Compostos Radiofarmacêuticos/imunologia , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Fragmentos Fab das Imunoglobulinas/química , Marcação por Isótopo/métodos , Camundongos SCID , Tomografia por Emissão de Pósitrons/métodos , Estudo de Prova de Conceito , Compostos Radiofarmacêuticos/química , Ratos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA