In vivo biodistribution and lifetime analysis of Cy5.5-conjugated rituximab in mice bearing lymphoid tumor xenograft using time-domain near-infrared optical imaging

Stefania Biffi, Chiara Garrovo, Paolo Macor, Claudio Tripodo, Sonia Zorzet, Erika Secco, Francesco Tedesco, Vito Lorusso

Research output: Contribution to journalArticle

Abstract

Rituximab is a chimeric monoclonal antibody directed against human CD20 antigen, which is expressed on B-cell lympho cytes and on the majority of B-cell lymphoid malignancies. Herein we report the conjugate of rituximab with the near-infrared (NIR) fluorophore Cy5.5 (RI-Cy5.5) as a tool for in vitro, in vivo, and ex vivo NIR time-domain (TD) optical imaging. In vitro, RI-Cy5.5 retained biologic activity and led to elevated cell-associated fluorescence on tumor cells. In vivo, TD optical imaging analysis of RI-Cy5.5 injected into lymphoma-bearing mice revealed a slow tumor uptake and a specific long-lasting persistence of the probe within the tumor. Biodistribution studies after intraperitoneal and endovenous administration were undertaken to evaluate differences in the tumor uptake. RI-Cy5.5 concentration in the organs after intraperitoneal injection was not as high as after endovenous injection. Ex vivo analysis of biologic tissues and organs by both TD optical imaging and immunohistochemistry confirmed the probe distribution, as demonstrated by imaging experiment in vivo, showing that RI-Cy5.5 selectively accumulated in the tumor tissue and major excretion organs. In summary, the study indicates that NIR TD optical imaging is a powerful tool for rituximab-targeting investigation, furthering understanding of its administration outcome in lymphoma treatment.

Original languageEnglish
Pages (from-to)272-282
Number of pages11
JournalMolecular Imaging
Volume7
Issue number6
DOIs
Publication statusPublished - Nov 2008

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Bearings (structural)
Optical Imaging
Heterografts
mice
Tumors
tumors
Infrared radiation
Imaging techniques
life (durability)
organs
Cells
Neoplasms
Lymphoma
Tissue
injection
B-Lymphocytes
CD20 Antigens
excretion
Monoclonal antibodies
Fluorophores

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging
  • Condensed Matter Physics

Cite this

In vivo biodistribution and lifetime analysis of Cy5.5-conjugated rituximab in mice bearing lymphoid tumor xenograft using time-domain near-infrared optical imaging. / Biffi, Stefania; Garrovo, Chiara; Macor, Paolo; Tripodo, Claudio; Zorzet, Sonia; Secco, Erika; Tedesco, Francesco; Lorusso, Vito.

In: Molecular Imaging, Vol. 7, No. 6, 11.2008, p. 272-282.

Research output: Contribution to journalArticle

Biffi, Stefania ; Garrovo, Chiara ; Macor, Paolo ; Tripodo, Claudio ; Zorzet, Sonia ; Secco, Erika ; Tedesco, Francesco ; Lorusso, Vito. / In vivo biodistribution and lifetime analysis of Cy5.5-conjugated rituximab in mice bearing lymphoid tumor xenograft using time-domain near-infrared optical imaging. In: Molecular Imaging. 2008 ; Vol. 7, No. 6. pp. 272-282.
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