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Radiolabeled F(ab')2-cetuximab for theranostic purposes in colorectal and skin tumor-bearing mice models
Bellaye, PS; Moreau, M; Raguin, O; Oudot, A; Bernhard, C; Vrigneaud, JM; Dumont, L; Vandroux, D; Denat, F; Cochet, A; Brunotte, F; Collin, B.
Afiliação
  • Bellaye, PS; Centre Georges-François Leclerc. Service de Médecine Nucléaire. Dijon. France
  • Moreau, M; Université de Bourgogne. Institut de Chimie Moléculaire. Dijon. France
  • Raguin, O; Oncodesign. Dijon. France
  • Oudot, A; Centre Georges-François Leclerc. Service de médecine nucléaire. Dijon. France
  • Bernhard, C; Université de Bourgogne. Institut de Chimie Moléculaire. Dijon. France
  • Vrigneaud, JM; Centre Georges-François Leclerc. Service de médecine nucléaire. Dijon. France
  • Dumont, L; NVH Medicinal. Dijon. France
  • Vandroux, D; NVH Medicinal. Dijon. France
  • Denat, F; Université de Bourgogne. Institut de Chimie Moléculaire. Dijon. France
  • Cochet, A; Centre Georges-François Leclerc. Service de médecine nucléaire. Dijon. France
  • Brunotte, F; Centre Georges-François Leclerc. Service de médecine nucléaire. Dijon. France
  • Collin, B; Centre Georges-François Leclerc. Service de médecine nucléaire. Dijon. France
Clin. transl. oncol. (Print) ; 20(12): 1557-1570, dic. 2018. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-173762
Biblioteca responsável: ES1.1
Localização: BNCS
ABSTRACT

Purpose:

This study aimed to investigate theranostic strategies in colorectal and skin cancer based on fragments of cetuximab, an anti-EGFR mAb, labeled with radionuclide with imaging and therapeutic properties, 111In and 177Lu, respectively.

Methods:

We designed F(ab′)2-fragments of cetuximab radiolabeled with 111In and 177Lu. 111In-F(ab′)2-cetuximab tumor targeting and biodistribution were evaluated by SPECT in BalbC nude mice bearing primary colorectal tumors. The efficacy of 111In-F(ab′)2-cetuximab to assess therapy efficacy was performed on BalbC nude mice bearing colorectal tumors receiving 17-DMAG, an HSP90 inhibitor. Therapeutic efficacy of the radioimmunotherapy based on 177Lu-F(ab′)2-cetuximab was evaluated in SWISS nude mice bearing A431 tumors.

Results:

Radiolabeling procedure did not change F(ab′)2-cetuximab and cetuximab immunoreactivity nor affinity for HER1 in vitro. 111In-DOTAGA-F(ab′)2-cetuximab exhibited a peak tumor uptake at 24 h post-injection and showed a high tumor specificity determined by a significant decrease in tumor uptake after the addition of an excess of unlabeled-DOTAGA-F(ab′)2-cetuximab. SPECT imaging of 111In-DOTAGA-F(ab′)2-cetuximab allowed an accurate evaluation of tumor growth and successfully predicted the decrease in tumor growth induced by 17-DMAG. Finally, 177Lu-DOTAGA-F(ab′)2-cetuximab radioimmunotherapy showed a significant reduction of tumor growth at 4 and 8 MBq doses.

Conclusions:

111In-DOTAGA-F(ab′)2-cetuximab is a reliable and stable tool for specific in vivo tumor targeting and is suitable for therapy efficacy assessment. 177Lu-DOTAGA-F(ab′)2-cetuximab is an interesting theranostic tool allowing therapy and imaging
RESUMEN
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Assuntos

Texto completo: Disponível Coleções: Bases de dados nacionais / Espanha Base de dados: IBECS Assunto principal: Neoplasias Cutâneas / Neoplasias Colorretais / Radioimunoterapia / Cetuximab / Nanomedicina Teranóstica Tipo de estudo: Estudo prognóstico Limite: Animais Idioma: Inglês Revista: Clin. transl. oncol. (Print) Ano de publicação: 2018 Tipo de documento: Artigo Instituição/País de afiliação: Centre Georges-François Leclerc/France / NVH Medicinal/France / Oncodesign/France / Université de Bourgogne/France

Texto completo: Disponível Coleções: Bases de dados nacionais / Espanha Base de dados: IBECS Assunto principal: Neoplasias Cutâneas / Neoplasias Colorretais / Radioimunoterapia / Cetuximab / Nanomedicina Teranóstica Tipo de estudo: Estudo prognóstico Limite: Animais Idioma: Inglês Revista: Clin. transl. oncol. (Print) Ano de publicação: 2018 Tipo de documento: Artigo Instituição/País de afiliação: Centre Georges-François Leclerc/France / NVH Medicinal/France / Oncodesign/France / Université de Bourgogne/France
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