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Biodistribution and PET Imaging of a Novel [68Ga]-Anti-CD163-Antibody Conjugate in Rats with Collagen-Induced Arthritis and in Controls

Abstract

Purpose

The hemoglobin scavenger receptor CD163 is exclusively expressed on monocytes and tissue macrophages, also at sites of inflammation. We examined whether gallium-68 (Ga-68)-labeled anti-CD163-antibody can detect the receptor in vivo.

Procedures

We radiolabeled anti-CD163 antibody with Ga-68 and evaluated stability and binding specificity of the conjugate ([68Ga]ED2) in vitro. Furthermore, tracer biodistribution was assessed in vivo in healthy rats and rats with acute collagen-induced arthritis (CIA) by MicroPET and tissue analysis.

Results

Radiosynthesis of [68Ga]ED2 antibody yielded a tracer with high-specific activity and radiochemical purity. [68Ga]ED2 bound specifically to CD163 in vitro. In rats, [68Ga]ED2 rapidly accumulated in macrophage-rich tissues. The arthritic paws exhibited a low but significant [68Ga]ED2 uptake. Interestingly, the systemic distribution was also changed in the sense that a significantly higher liver uptake and lower spleen uptake of [68Ga]ED2 was measured in CIA rats that accordingly showed a corresponding change in level of CD163 expression.

Conclusions

[68Ga]ED2 specifically binds CD163 in vitro and in vivo. Biodistribution studies in CIA rats suggest that this novel tool may have applications in studies of inflammatory diseases.

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Acknowledgments

This study has been financially supported by an ERC grant for the TROJA project (Project 233312 Targeting Receptors Of Jointly Assembled Drug-Ligand Complexes) as well as a Mobility Ph.D. fellowship to Sascha Eichendorff from Aarhus University. Bent Deleuran was supported by the Danish Rheumatoid Association.

The authors wish to thank Mette Simonsen from the Department of Nuclear Medicine & PET Centre, Aarhus University Hospital for skillful assistance with MicroPET imaging and biodistribution experiments. Karina Højrup Vase and Lykke Hagelskjær Pedersen, also from the Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, were of great help with the gallium generator handling.

Conflict of Interest

The authors state that they have no conflicts of interest.

Author information

Correspondence to Søren K. Moestrup.

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Eichendorff, S., Svendsen, P., Bender, D. et al. Biodistribution and PET Imaging of a Novel [68Ga]-Anti-CD163-Antibody Conjugate in Rats with Collagen-Induced Arthritis and in Controls. Mol Imaging Biol 17, 87–93 (2015). https://doi.org/10.1007/s11307-014-0768-6

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Key words

  • CD163
  • Positron emission tomography
  • Arthritis
  • Macrophages
  • Liver