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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 27-08-2022 | Original Article

Quantitative PET imaging of the CD4 pool in nonhuman primates

Authors: Insook Kim, Sharat Srinivasula, Paula DeGrange, Brad Long, Hyukjin Jang, Jorge A. Carrasquillo, H. Clifford Lane, Michele Di Mascio

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 1/2022

Abstract

Purpose

Previous SPECT and PET semi-quantitative in vivo imaging studies in monkeys have demonstrated specific uptake of radiolabeled rhesus recombinant anti-CD4 monoclonal antibody fragment CD4R1-F(ab΄)₂ in the spleen and clusters of lymph nodes (LNs) but yielded conflicting results of imaging the gut CD4 + T-cell pool. Here, using PET dynamic imaging with kinetic analysis, we performed a fully quantitative CD4 imaging in rhesus macaques.

Methods

The biodistributions of [⁸⁹Zr]Zr-CD4R1-F(ab΄)₂ and/or of [⁸⁹Zr]Zr-ibalizumab were performed with static PET scans up to 144 h (6 days) post-injection in 18 rhesus macaques with peripheral blood CD4 + T cells/μl ranging from ~ 20 to 2400. Fully quantitative analysis with a 4-h dynamic scan, arterial sampling, metabolite evaluation, and model fitting was performed in three immunocompetent monkeys to estimate the binding potential of CD4 receptors in the LNs, spleen, and gut.

Results

The biodistributions of [⁸⁹Zr]Zr-CD4R1-F(ab΄)₂ and [⁸⁹Zr]Zr-ibalizumab were similar in lymphoid tissues with a clear delineation of the CD4 pool in the LNs and spleen and a significant difference in lymphoid tissue uptake between immunocompetent and immunocompromised macaques. Consistent with our previous SPECT imaging of [^99mTc]Tc-CD4R1-F(ab΄)₂, the [⁸⁹Zr]Zr-CD4R1-F(ab΄)₂ and [⁸⁹Zr]Zr-Ibalizumab uptakes in the gut were low and not different between uninfected and SIV-infected CD4-depleted monkeys. Ex vivo studies of large and small intestines confirmed the in vivo images.

Conclusion

The majority of specific binding to CD4 + tissue was localized to LNs and spleen with minimal uptake in the gut. Binding potential derived from fully quantitative studies revealed that the contribution of the gut is lower than the spleen’s contribution to the total body CD4 pool.

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Title: Quantitative PET imaging of the CD4 pool in nonhuman primates
Authors: Insook Kim
Sharat Srinivasula
Paula DeGrange
Brad Long
Hyukjin Jang
Jorge A. Carrasquillo
H. Clifford Lane
Michele Di Mascio
Publication date: 27-08-2022
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 1/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-022-05940-4

At a glance: The STEP trials

Springer Medicine

Quantitative PET imaging of the CD4 pool in nonhuman primates

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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