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

  • Janie Duvenhage
  • Thomas Ebenhan
  • Seike Garny
  • Ignacio Hernández González
  • René Leyva Montaña
  • Roger Price
  • Lyn-Marie Birkholtz
  • Jan Rijn ZeevaartEmail author
Research Article

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.

Key words

Plasmodium falciparum Micro-PET/CT imaging [89Zr]IIIB6 Nimotuzumab Zirconium-89 

Notes

Acknowledgements

Cor Bester (Preclinical Drug Development Platform North West University) is thanked for assisting with the animal handling and Delene van Wyk (Steve Biko Academic Hospital) for assisting with the scintigraphic imaging.

Funding Information

This work was supported by the Nuclear Technologies in Medicine and the Biosciences Initiative (NTeMBI), a national technology platform developed and managed by the South African Nuclear Energy Corporation (Necsa) and funded by the Department of Science and Technology to JD, TE and JZ. LB received funding from the South African Research Chairs Initiative of the Department of Science and Technology, administered through the South African National Research Foundation (UID84627).

Compliance with Ethical Standards

All procedures relating to the [89Zr]IIIB6 study were approved by North West University’s AnimCare Ethical Committee (NWU-00042-12-A5). All procedures involving the [89Zr]h-R3 were approved by the Animal Ethics Committee (AEC) of University of Western Australia (RA/3/100/1236). Ethical approval for the in vitro studies was granted by the University of Pretoria Ethical committee (No.: 120821-077).

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© World Molecular Imaging Society 2019

Authors and Affiliations

  • Janie Duvenhage
    • 1
    • 2
  • Thomas Ebenhan
    • 2
    • 3
  • Seike Garny
    • 1
  • Ignacio Hernández González
    • 4
  • René Leyva Montaña
    • 5
  • Roger Price
    • 6
    • 7
  • Lyn-Marie Birkholtz
    • 1
  • Jan Rijn Zeevaart
    • 2
    • 8
    Email author
  1. 1.Department of Biochemistry, Genetics and Microbiology, Institute of Sustainable Malaria ControlUniversity of PretoriaPretoriaSouth Africa
  2. 2.Preclinical Imaging FacilityThe South African Nuclear Energy Corporation SOC Ltd (Necsa)PelindabaSouth Africa
  3. 3.Department of Nuclear MedicineUniversity of PretoriaPretoriaSouth Africa
  4. 4.Department of DevelopmentCenter of IsotopesHavanaCuba
  5. 5.Deparment of RadiopharmacyCenter of IsotopesHavanaCuba
  6. 6.Department of PhysicsUniversity of Western AustraliaPerthAustralia
  7. 7.Rapid LaboratoriesSir Charles Gairdner HospitalPerthAustralia
  8. 8.Preclinical Drug Development PlatformNorth West UniversityPotchefstroomSouth Africa

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