Share Email Print
cover

Journal of Biomedical Optics • Open Access

Activatable fluorescent cys-diabody conjugated with indocyanine green derivative: consideration of fluorescent catabolite kinetics on molecular imaging
Author(s): Kohei Sano; Takahito Nakajima; Towhid Ali; Derek W. Bartlett; Anna M. Wu; Insook Kim; Chang H. Paik; Peter Choyke; Hisataka Kobayashi

Paper Abstract

Antibody fragments including diabodies have more desirable pharmacokinetic characteristics than whole antibodies. An activatable optical imaging probe based on a cys-diabody targeting prostate-specific membrane antigen conjugated with the near-infrared fluorophore, indocyanine green (ICG), was designed such that it can only be activated when bound to the tumor, leading to high signal-to-background ratios. We employed short polyethylene glycol (PEG) linkers between the ICG and the reactive functional group (Sulfo-OSu group), resulting in covalent conjugation of ICG to the cys-diabody, which led to lower dissociation of ICG from cys-diabody early after injection, reducing hepatic uptake. However, unexpectedly, high and long-term fluorescence was observed in the kidneys, liver, and blood pool more than 1 h after injection of the cys-diabody PEG-ICG conjugate. A biodistribution study using I 125 -labeled cys-diabody-ICG showed immediate uptake in the kidneys followed by a rapid decrease, while gastric activity increased due to released radioiodine during rapid cys-diabody-ICG catabolism in the kidneys. To avoid this catabolic pathway, it would be preferable to use antibody fragments large enough not to be filtered through glomerulus or to conjugate the fragments with fluorescent dyes that are readily excreted into urine when cleaved from the cys-diabody to achieve high tumor-specific detection.

Paper Details

Date Published: 10 June 2013
PDF: 7 pages
J. Biomed. Opt. 18(10) 101304 doi: 10.1117/1.JBO.18.10.101304
Published in: Journal of Biomedical Optics Volume 18, Issue 10
Show Author Affiliations
Kohei Sano, National Cancer Institute (United States)
Takahito Nakajima, National Institutes of Health (United States)
Towhid Ali, National Institutes of Health (United States)
Derek W. Bartlett, ImaginAb (United States)
Anna M. Wu, Univ. of California, Los Angeles (United States)
Insook Kim, SAIC-Frederick, Inc. (United States)
Chang H. Paik, National Institutes of Health (United States)
Peter Choyke, National Institutes of Health (United States)
Hisataka Kobayashi, National Institutes of Health (United States)


© SPIE. Terms of Use
Back to Top