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1.
Eur J Nucl Med Mol Imaging ; 50(3): 870-880, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36305908

RESUMO

PURPOSE: Sentinel lymph node (SLN) biopsy is a staging procedure in the management of cutaneous malignancies of the head. The ideal radiopharmaceutical is controversial. This study aimed to compare [99mTc]Tc-tilmanocept (TcTM) with [99mTc]Tc-sulphur colloid (TcSC) and [99mTc]Tc-albumin colloid (TcAC) for SLN detection in the head and neck region. METHODS: Data from 62 patients with cutaneous malignancies of the head who were injected with TcTM, TcSC, or TcAC before SLN imaging (SLN-I) and SLN excision (SLN-E) between 2012 and 2021 were retrospectively analysed. SLN-I was performed using planar lymphoscintigraphy and SPECT/CT, and a gamma probe was used for SLN-E. The SLN-I localisation rate (patients with SLNs) and degree (SLN number) and SLN-E relocalisation rate (patients with SLNs) and ratio (SLN number in SLN-E/SLN number in SLN-I) were compared between TcTM, TcSC, and TcAC. RESULTS: TcTM showed similar SLN-I localisation rates for primaries in the anterior and posterior head region compared with TcSC (84.6% vs. 72.4%, p=0.680; both 100.0%) and TcAC (84.6% vs. 75.0%, p=1.000; both 100.0%). The SLN-I localisation degree for TcTM was higher for primaries in the anterior head region and similar for primaries in the posterior head region compared with TcSC (3.2 vs. 2.3, p=0.034; and 1.8 vs. 2.2, p=0.506) and TcAC (3.2 vs. 2.0, p=0.038; and 1.8 vs. 2.7, p=0.329). The SLN-E relocalisation rates and ratios were similar for all. CONCLUSION: On the basis of a limited study design that compared three different tracers in three different patient groups, TcTM showed comparable overall performance to TcSC and TcAC.


Assuntos
Neoplasias da Mama , Linfonodo Sentinela , Neoplasias Cutâneas , Humanos , Feminino , Linfonodo Sentinela/diagnóstico por imagem , Pentetato de Tecnécio Tc 99m , Estudos Retrospectivos , Compostos Radiofarmacêuticos , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Albuminas , Enxofre , Linfonodos/patologia , Neoplasias da Mama/patologia
2.
Mol Imaging Biol ; 22(3): 623-633, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31396770

RESUMO

PURPOSE: Evaluation of [68Ga]NODAGA-duramycin as a positron emission tomography (PET) tracer of cell death for whole-body detection of chemotherapy-induced organ toxicity. PROCEDURES: Tracer specificity of Ga-68 labeled NODAGA-duramycin was determined in vitro using competitive binding experiments. Organ uptake was analyzed in untreated and doxorubicin, busulfan, and cisplatin-treated mice 2 h after intravenous injection of [68Ga]NODAGA-duramycin. In vivo data were validated by immunohistology and blood parameters. RESULTS: In vitro experiments confirmed specific binding of [68Ga]NODAGA-duramycin. Organ toxicities were detected successfully using [68Ga]NODAGA-duramycin PET/X-ray computed tomography (CT) and confirmed by immunohistochemistry and blood parameter analysis. Organ toxicities in livers and kidneys showed similar trends in PET/CT and immunohistology. Busulfan and cisplatin-related organ toxicities in heart, liver, and lungs were detected earlier by PET/CT than by blood parameters and immunohistology. CONCLUSION: [68Ga]NODAGA-duramycin PET/CT was successfully applied to non-invasively detect chemotherapy-induced organ toxicity with high sensitivity in mice. It, therefore, represents a promising alternative to standard toxicological analyses with a high translational potential.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bacteriocinas , Radioisótopos de Gálio , Rim/efeitos dos fármacos , Rim/diagnóstico por imagem , Fígado/efeitos dos fármacos , Fígado/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Peptídeos , Acetatos/química , Acetatos/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bacteriocinas/química , Bacteriocinas/farmacocinética , Bussulfano/administração & dosagem , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Radioisótopos de Gálio/química , Radioisótopos de Gálio/farmacocinética , Compostos Heterocíclicos com 1 Anel/química , Compostos Heterocíclicos com 1 Anel/metabolismo , Rim/metabolismo , Rim/patologia , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/patologia , Peptídeos/química , Peptídeos/farmacocinética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual
3.
Cancer Med ; 6(7): 1639-1651, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28608446

RESUMO

Here, we examined the potential of blocking the thymidine de novo synthesis pathways for sensitizing melanoma cells to the nucleoside salvage pathway targeting endogenous DNA irradiation. Expression of key nucleotide synthesis and proliferation enzymes thymidylate synthase (TS) and thymidine kinase 1 (TK1) was evaluated in differentiated (MITFhigh [microphthalmia-associated transcription factor] IGR1) and invasive (MITFmedium IGR37) melanoma cells. For inhibition of de novo pathways cells were incubated either with an irreversible TS inhibitor 5-fluoro-2'-deoxyuridine (FdUrd) or with a competitive dihydrofolate-reductase (DHFR) inhibitor methotrexate (MTX). Salvage pathway was addressed by irradiation-emitting thymidine analog [123/125 I]-5-iodo-4'-thio-2'-deoxyuridine (123/125 I-ITdU). The in vivo targeting efficiency was visualized by single-photon emission computed tomography. Pretreatment with FdUrd strongly increased the cellular uptake and the DNA incorporation of 125 I-ITdU into the mitotically active IGR37 cells. This effect was less pronounced in the differentiated IGR1 cells. In vivo, inhibition of TS led to a high and preferential accumulation of 123 I-ITdU in tumor tissue. This preclinical study presents profound rationale for development of therapeutic approach by highly efficient and selective radioactive targeting one of the crucial salvage pathways in melanomas.


Assuntos
Antineoplásicos/farmacologia , Vias Biossintéticas/efeitos dos fármacos , Melanoma/metabolismo , Timidina/biossíntese , Animais , Antineoplásicos/uso terapêutico , Biomarcadores , Vias Biossintéticas/efeitos da radiação , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Glutationa/metabolismo , Humanos , Radioisótopos do Iodo , Melanoma/diagnóstico por imagem , Melanoma/tratamento farmacológico , Melanoma/patologia , Camundongos , Mitose/efeitos dos fármacos , Mitose/genética , Imagem Molecular , Terapia de Alvo Molecular , Nucleosídeos/metabolismo , Oxirredução , Radiação , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação
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