Purpose: Nuclear imaging is an important pre-clinical 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), it's 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-PET/CT imaging, IIIB6 was conjugated to Bz-DFO-NCS and subsequently radiolabeled with zirconium-89.Healthy nude mice were injected with [ 89 Zr]IIIB6 and pharmacokinetics and organ uptake were monitored over 24 hours. This was followed by post mortem animal dissection to determine the biodistribution of [ 89 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. [ 89 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 [ 89 Zr]IIIB6. The highest standard uptake values were determined at 2-6 h in the liver followed by the spleen, kidneys, heart, stomach, lung, respectively. Minimal activity was present in muscle-and bone tissue.
Conclusion:In vitro characterisation of IIIB6 and pharmacokinetic characterization of [ 89 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.