Zr-89-DFO-cetuximab as a molecular imaging agent to identify cetuximab resistance in head and neck squamous cell carcinoma
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2019
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Cancer Biotherapy and Radiopharmaceuticals
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Background: Despite the improvement in clinical outcomes for head and neck squamous cell carcinoma
(HNSCC) as the result of cetuximab, patients may present with or develop resistance that increases tumor
recurrence rates and limits clinical efficacy. Therefore, identifying those patients who are or become resistant is
essential to tailor the best therapeutic approach.
Materials and Methods: Cetuximab was conjugated to p-NCS-Bz-DFO and labeled with 89Zr. The resistance
model was developed by treating FaDu cells with cetuximab. Western blotting (WB) and specific binding assays
were performed to evaluate epidermal growth factor receptor (EGFR) expression and 89Zr-DFO-cetuximab uptake
in FaDu cetuximab-resistant (FCR) and FaDu cetuximab-sensitive (FCS) cells. Positron emission tomography
imaging and biodistribution were conducted in NU/NU nude mice implanted with FCR or FCS cells.
Results: Cetuximab was successfully radiolabeled with 89Zr (‡95%). Binding assays performed in FCR and
FCS cells showed significantly lower 89Zr-DFO-cetuximab uptake in FCR ( p < 0.0001). WB suggests that the
resistance mechanism is associated with EGFR downregulation ( p = 0.038). This result is in agreement with the
low uptake of 89Zr-DFO-cetuximab in FCR cells. Tumor uptake of 89Zr-DFO-cetuximab in FCR was significantly
lower than FCS tumors ( p = 0.0340).
Conclusions: In this work, the authors showed that 89Zr-DFO-cetuximab is suitable for identification of EGFR
downregulation in vitro and in vivo. This radiopharmaceutical may be useful for monitoring resistance in
HNSCC patients during cetuximab therapy.
Como referenciar
BENEDETTO, RAQUEL; MASSICANO, ADRIANA V.F.; CRENSHAW, BRYANT K.; OLIVEIRA, RENATO; REIS, RUI M.; ARAUJO, ELAINE B.; LAPI, SUZANNE E. Zr-89-DFO-cetuximab as a molecular imaging agent to identify cetuximab resistance in head and neck squamous cell carcinoma. Cancer Biotherapy and Radiopharmaceuticals, v. 34, n. 5, p. 288-296, 2019. DOI: 10.1089/cbr.2018.2616. Disponível em: http://repositorio.ipen.br/handle/123456789/30058. Acesso em: 25 Apr 2024.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.