99mTc-HYNIC/Cy7-Fab(Bevacizumab): its use as an imaging agent in Multiple Myeloma.
DOI:
https://doi.org/10.35954/SM2023.42.1.4.e302Keywords:
Fab(Bevacizumab), Vascular Endothelial Growth Factor, Molecular Imaging, Multiple Myeloma, 99mTecnetium.Abstract
Introduction: Multiple myeloma is a hematologic malignancy and the second most common blood cancer. The process of tumor angiogenesis is central to the growth and metastasis of many types of tumors, including multiple myeloma. Overexpression of vascular endothelial growth factor is known to be associated with poor prognosis in this pathology, representing a key target for anti-angiogenic therapy in multiple myeloma. The monoclonal antibody Bevacizumab is able to bind with high affinity to vascular endothelial growth factor blocking its action.
Objective: to evaluate 99mTc- or Cy7-labeled Fab(Bevacizumab) as potential molecular imaging agents of vascular endothelial growth factor expression in multiple myeloma.
Methods: Vascular endothelial growth factor expression was analyzed by flow cytometry in the multiple myeloma huaman cell line, MM1S. Fab(Bevacizumab) was produced by digestion of Bevacizumab with papain, conjugated to NHS-HYNIC-Tfa and radiolabeled with 99mTc. Biodistribution and single photon emission computed tomography studies were performed. In turn, Fab(Bevacizumab) was labeled with Cy7 to obtain in vivo fluorescence images up to 96 hours.
Results: Flow cytometry analysis in the MM1S cell line revealed that vascular endothelial growth factor expression is predominantly intracellular. Biodistribution and SPECT/CT studies of the 99mTc-HYNIC-Fab(Bevacizumab) complex showed rapid blood clearance and significant renal and tumor uptake. Fluorescence imaging using Cy7-Fab(Bevacizumab) allowed tumor visualization up to 96 h p.i.
Conclusions: we were able to visualize vascular endothelial growth factor expression in vivo in multiple myeloma using the Fab fragment of the anti-VEGF antibody (Bevacizumab) labeled with 99mTc and Cy7. These new molecular imaging agents could potentially be employed in the clinical setting for staging and monitoring of patients with multiple myeloma by in vivo radioactive visualization of vascular endothelial growth factor expression throughout the body. Optical imaging of these tracers would improve tumor sampling and could guide surgical excision.
Received for review: January 2023.
Accepted for publication: March 2023.
Correspondence: Ximena Camacho. Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay. Mataojo 2055, C.P. 11400, Montevideo, Uruguay. Tel: (+598) 294921199.
Contact e-mail: xcamacho@cin.edu.uy
This article was approved by the Editorial Committee.
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Copyright (c) 2023 Ximena Camacho, Carolina Perroni, Mirel Cabrera, Marcos Tassano, Camila Longo Machado, Camila de Godoi Carneiro, Mara de Souza Junqueira, Daniele Faria, María Fernanda García, Marcelo Fernández, Carlos Buchpiguel, Hugo Cerecetto, Roger Chamas, Eloisa Riva, Juan Pablo Gambini, Pablo Cabral. The author retains his copyright and assigns to the journal the right of first publication of his work, which will be simultaneously subject to the Creative Commons Attribution 4.0 International License that allows sharing the work as long as the initial publication in this journal is indicated.
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