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PET/CT Imaging of Human TNFα Using [89Zr]Certolizumab Pegol in a Transgenic Preclinical Model of Rheumatoid Arthritis.
Beckford-Vera, Denis R; Gonzalez-Junca, Alba; Janneck, Jessica S; Huynh, Tony L; Blecha, Joseph E; Seo, Youngho; Li, Xiaojuan; VanBrocklin, Henry F; Franc, Benjamin L.
Afiliación
  • Beckford-Vera DR; Department of Radiology and Molecular Imaging, University of California San Francisco, 185 Berry St., Suite 350, San Francisco, CA, 94107, USA. denis.beckfordvera@ucsf.edu.
  • Gonzalez-Junca A; Department of Radiation Oncology, University of California San Francisco, 2340 Sutter St., San Francisco, CA, 94115, USA.
  • Janneck JS; Department of Radiology and Molecular Imaging, University of California San Francisco, 185 Berry St., Suite 350, San Francisco, CA, 94107, USA.
  • Huynh TL; Department of Radiology and Molecular Imaging, University of California San Francisco, 185 Berry St., Suite 350, San Francisco, CA, 94107, USA.
  • Blecha JE; Department of Radiology and Molecular Imaging, University of California San Francisco, 185 Berry St., Suite 350, San Francisco, CA, 94107, USA.
  • Seo Y; Department of Radiology and Molecular Imaging, University of California San Francisco, 185 Berry St., Suite 350, San Francisco, CA, 94107, USA.
  • Li X; Department of Radiology and Molecular Imaging, University of California San Francisco, 185 Berry St., Suite 350, San Francisco, CA, 94107, USA.
  • VanBrocklin HF; Department of Radiology and Molecular Imaging, University of California San Francisco, 185 Berry St., Suite 350, San Francisco, CA, 94107, USA.
  • Franc BL; Department of Radiology and Molecular Imaging, University of California San Francisco, 185 Berry St., Suite 350, San Francisco, CA, 94107, USA.
Mol Imaging Biol ; 22(1): 105-114, 2020 02.
Article en En | MEDLINE | ID: mdl-31065895
PURPOSE: Tumor necrosis factor alpha (TNFα) drives inflammation and bone degradation in patients with rheumatoid arthritis (RA). Some RA patients experience a rapid clinical response to TNFα inhibitors such as certolizumab pegol (CZP) while other patients show limited to no response. Current methods for imaging RA have limited sensitivity and do not assist in the selection of patients most likely to respond to immune-mediated therapy. Herein, we developed a novel positron emission tomography (PET) radiotracer for immuno-PET imaging of TNFα in transgenic human TNFα-expressing mice. PROCEDURES: CZP was modified with p-isothiocyanatobenzyl-deferoxamine (DFO) and radiolabeled with Zr-89. The biological activity of [89Zr]DFO-CZP was evaluated by HPLC and binding assay using human recombinant TNFα (hTNFα). The feasibility of specific immuno-PET imaging of human TNFα was assessed in a transgenic mouse model of RA that expresses human TNFα. This model resembles the progression of RA in humans by maintaining lower levels of circulating hTNFα and exhibits chronic arthritis in the forepaw and hind paw joints. The dosimetry of [89Zr]DFO-CZP in humans was estimated using microPET/CT imaging in Sprague Dawley rats. RESULTS: [89Zr]DFO-CZP was isolated with radiolabeling yields of 85 ± 6 % (n = 5) and specific activities ranging from 74 to 185 MBq/mg (n = 5). Following size exclusion purification, the radiochemical purity of [89Zr]DFO-CZP was greater than 97 %. [89Zr]DFO-CZP retained high immunoreactivity with more than 95 % of the radioactivity shifted into higher molecular weight complexes. Images showed increasing uptake of the tracer in forepaw and hind paw joints with disease progression. No uptake was observed in the model previously administered with an excess amount of unmodified CZP and in normal control mice, demonstrating in vivo specific uptake of [89Zr]DFO-CZP. CONCLUSION: The feasibility of immuno-PET imaging of human TNFα with [89Zr]DFO-CZP has been demonstrated in a preclinical model of RA.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Experimental / Artritis Reumatoide / Radioisótopos / Circonio / Factor de Necrosis Tumoral alfa / Inmunoconjugados / Certolizumab Pegol / Tomografía Computarizada por Tomografía de Emisión de Positrones Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Mol Imaging Biol Asunto de la revista: BIOLOGIA MOLECULAR / DIAGNOSTICO POR IMAGEM Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Experimental / Artritis Reumatoide / Radioisótopos / Circonio / Factor de Necrosis Tumoral alfa / Inmunoconjugados / Certolizumab Pegol / Tomografía Computarizada por Tomografía de Emisión de Positrones Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Mol Imaging Biol Asunto de la revista: BIOLOGIA MOLECULAR / DIAGNOSTICO POR IMAGEM Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos