Janie Duvenhage1,2, Thomas Ebenhan2,3, Seike Garny1, Ignacio Hernández González4, René Leyva Montaña5, Roger Price6,7, Lyn-Marie Birkholtz1, Jan Rijn Zeevaart8,9. 1. Department of Biochemistry, Genetics and Microbiology, Institute of Sustainable Malaria Control, University of Pretoria, Pretoria, South Africa. 2. Preclinical Imaging Facility, The South African Nuclear Energy Corporation SOC Ltd (Necsa), Pelindaba, South Africa. 3. Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa. 4. Department of Development, Center of Isotopes, Havana, Cuba. 5. Deparment of Radiopharmacy, Center of Isotopes, Havana, Cuba. 6. Department of Physics, University of Western Australia, Perth, Australia. 7. Rapid Laboratories, Sir Charles Gairdner Hospital, Perth, Australia. 8. Preclinical Imaging Facility, The South African Nuclear Energy Corporation SOC Ltd (Necsa), Pelindaba, South Africa. janrijn.zeevaart@necsa.co.za. 9. Preclinical Drug Development Platform, North West University, Potchefstroom, South Africa. janrijn.zeevaart@necsa.co.za.
Abstract
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 [89Zr]IIIB6, and pharmacokinetics and organ uptake were monitored over 24 h. This was followed by post-mortem animal dissection to determine the biodistribution of [89Zr]IIIB6. RESULTS: IIIB6 recognised all the relevant stages of Plasmodium falciparum-infected erythrocytes (trophozoites, schizonts and gametocytes) that are responsible for severe malaria pathology. [89Zr]IIIB6-radiolabeling yields were efficient at 84-89 %. Blood pool imaging analysis indicated a pharmacological half-life of 9.6 ± 2.5 h for [89Zr]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 [89Zr]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.
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 [89Zr]IIIB6, and pharmacokinetics and organ uptake were monitored over 24 h. This was followed by post-mortem animal dissection to determine the biodistribution of [89Zr]IIIB6. RESULTS: IIIB6 recognised all the relevant stages of Plasmodium falciparum-infected erythrocytes (trophozoites, schizonts and gametocytes) that are responsible for severe malaria pathology. [89Zr]IIIB6-radiolabeling yields were efficient at 84-89 %. Blood pool imaging analysis indicated a pharmacological half-life of 9.6 ± 2.5 h for [89Zr]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 [89Zr]IIIB6 revealed that this antibody has potential for future use in Plasmodium-infectedmouse models to study malaria in a preclinical in vivo setting with PET/CT imaging.
Authors: Jason P Holland; Vadim Divilov; Neil H Bander; Peter M Smith-Jones; Steven M Larson; Jason S Lewis Journal: J Nucl Med Date: 2010-07-21 Impact factor: 10.057
Authors: Ursula Elsässer-Beile; Gerald Reischl; Stefan Wiehr; Patrick Bühler; Philipp Wolf; Karen Alt; John Shively; Martin S Judenhofer; Hans-Jürgen Machulla; Bernd J Pichler Journal: J Nucl Med Date: 2009-03-16 Impact factor: 10.057
Authors: Patrick J Madden; Muhammad S Arif; Mark E Becker; Michael D McRaven; Ann M Carias; Ramon Lorenzo-Redondo; Sixia Xiao; Cecily C Midkiff; Robert V Blair; Elizabeth Lake Potter; Laura Martin-Sancho; Alan Dodson; Elena Martinelli; John-Paul M Todd; Francois J Villinger; Sumit K Chanda; Pyone Pyone Aye; Chad J Roy; Mario Roederer; Mark G Lewis; Ronald S Veazey; Thomas J Hope Journal: Front Immunol Date: 2021-12-24 Impact factor: 7.561