Molecular Imaging of a Zirconium-89 Labeled Antibody Targeting Plasmodium falciparum-Infected Human Erythrocytes.

Authors:
Thomas Ebenhan
Thomas Ebenhan
University of Pretoria and Steve Biko Academic Hospital Private Bag X169 Pretoria
South Africa
Seike Garny
Seike Garny
University of Cape Town
South Africa
Ignacio Hernandez Gonzalez
Ignacio Hernandez Gonzalez
Hospital Universitario Fundación Jiménez Díaz
Roger Price
Roger Price
The University of Texas M. D. Anderson Cancer Center
United States
Jan Rijn Zeevaart
Jan Rijn Zeevaart
North West University
South Africa

Mol Imaging Biol 2019 Apr 19. Epub 2019 Apr 19.

Preclinical Imaging Facility, The South African Nuclear Energy Corporation SOC Ltd (Necsa), Pelindaba, South Africa.

Purpose: Nuclear imaging is an important preclinical research tool to study infectious diseases in vivo and could be extended to investigate complex aspects of malaria infections. As such, we report for the first time successful radiolabeling of a novel antibody specific to Plasmodium-infected erythrocytes (IIIB6), its in vitro assessment and molecular imaging in nude mice.

Procedures: In vitro confocal microscopy was used to determine the stage-specificity of Plasmodium-infected erythrocytes recognised by IIIB6. To enable micro-positron emission tomography (PET)/X-ray computed tomography (CT) imaging, IIIB6 was conjugated to Bz-DFO-NCS and subsequently radiolabeled with zirconium-89. Healthy nude mice were injected with [Zr]IIIB6, and pharmacokinetics and organ uptake were monitored over 24 h. This was followed by post-mortem animal dissection to determine the biodistribution of [Zr]IIIB6.

Results: IIIB6 recognised all the relevant stages of Plasmodium falciparum-infected erythrocytes (trophozoites, schizonts and gametocytes) that are responsible for severe malaria pathology. [Zr]IIIB6-radiolabeling yields were efficient at 84-89 %. Blood pool imaging analysis indicated a pharmacological half-life of 9.6 ± 2.5 h for [Zr]IIIB6. The highest standard uptake values were determined at 2-6 h in the liver followed by the spleen, kidneys, heart, stomach and lung, respectively. Minimal activity was present in muscle and bone tissues.

Conclusion: In vitro characterization of IIIB6 and pharmacokinetic characterization of [Zr]IIIB6 revealed that this antibody has potential for future use in Plasmodium-infected mouse models to study malaria in a preclinical in vivo setting with PET/CT imaging.

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http://link.springer.com/10.1007/s11307-019-01360-3
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http://dx.doi.org/10.1007/s11307-019-01360-3DOI Listing
April 2019
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References

(Supplied by CrossRef)
Article in Cell
AF Cowman et al.
Cell 2016
Article in Med Microbiol Immunol
N Mohandas et al.
Med Microbiol Immunol 2012
Article in Trends Parasitol
I Coppens et al.
Trends Parasitol 2010
Article in ILAR J
KR Zinn et al.
ILAR J 2008
Article in Malar J
RJ Maude et al.
Malar J 2014
Article in Clin Radiol
S Vaidyanathan et al.
Clin Radiol 2015
Article in Semin Nucl Med
M Sathekge et al.
Semin Nucl Med 2015
Article in Eur J Nucl Med Mol Imaging
M Sathekge et al.
Eur J Nucl Med Mol Imaging 2009
Article in Am J Trop Med Hyg
S Kawai et al.
Am J Trop Med Hyg 2006
Article in Am J Trop Med Hyg
M Sugiyama et al.
Am J Trop Med Hyg 2004
Article in Front Mol Neurosci
XY Zhang et al.
Front Mol Neurosci 2017

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