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Comparison of Invasive and Non-invasive Estimation of [11C]PBR28 Binding in Non-human Primates

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Abstract

Purpose

To identify a reliable alternative to the full blood [11C]PBR28 quantification method that would be easily replicated in multiple research and clinical settings.

Procedures

Ten [11C]PBR28 scans were acquired from 7 healthy non-human primates (NHP). Arterial input functions (AIFs) were averaged to create a population template input function (TIF). Population-based input functions were created by scaling the TIF with injected activity per body weight (PBIF) or unmetabolized tracer activity in blood at 15-,30-, and 60-min post-injection (PBIF15, PBIF30, and PBIF60). Two additional input functions were used: the native unmetabolized total plasma activity (Totals) and the Totals curve metabolite corrected by a scaled template parent fraction from a 30-min sample (TPF30-IF). Total distribution volumes (VTs) were calculated using PBIF, PBIF30, PBIF15, PBIF60, Totals, TPF30-IF, and the individual AIF (VTAIF). Distribution volume ratios (DVR) were computed using the cerebellum and the centrum semiovale (CSO), as pseudo-reference regions (DVRCereb, DVRCSO). Results obtained with each method were compared to VTAIF. Applicability of these alternative methods was tested on an independent pharmacological challenge dataset of microglial activation and depletion. Evaluation was carried at baseline, immediately after intervention (acute), and weeks post-intervention (post-recovery).

Results

VTs computed using PBIF15 and PBIF30 showed the best correlation to VTAIF (r > 0.90), while VT derived from the blood-free-scaled PBIF showed poor correlation (r = 0.46) and DVRCSO correlated the least (r = 0.26). In the pharmacological challenge study, most population-derived VT values were comparable to VTAIF at baseline and showed varied sensitivity to challenges at acute and post-recovery evaluation. DVR values did not detect relevant changes.

Conclusions

Population-based input functions scaled with a single blood sample might be a useful alternative to using AIF to compute [11C]PBR28 binding in healthy NHPs or animals with comparable metabolism and overall perform better than pseudo-reference regions approaches.

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Acknowledgements

We thank the UBC/TRIUMF PET program staff for their contribution to this work: this study would not have been possible without Carolyn English and Siobhan McCormick's assistance for the metabolite analyses radiochemistry laboratories at TRIUMF. Special thanks are due to Julian Kaye and the UBC Animal Care Facilities personnel for their animals' outstanding care. Finally, we thank Dr. Ansel Hillmer for providing the NHP data from Hillmer et al.[17] , and Dr. Richard Carson for an insightful discussion.

Funding

This work was supported by Brain Canada [F14-02712]. [11C]PBR28 was produced at TRIUMF, which is supported by the National Research Council of Canada.

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Authors and Affiliations

  1. Department of Medicine, Division of Neurology, University of British Columbia, Rm M36 Purdy Pavilion, 2221 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada

    Lucero Aceves-Serrano & Doris J. Doudet

  2. Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada

    Vesna Sossi

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  1. Lucero Aceves-Serrano
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Contributions

LAS performed experiments, conducted data analysis, and wrote the manuscript. VS discussed results and revised the manuscript. DJD designed the study, discussed results, and revised the manuscript. All authors edited the manuscript and approved the final submission.

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Correspondence to Lucero Aceves-Serrano.

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DJD is a Senior Editor for Molecular Imaging and Biology (Neurology). The authors declare that they have no conflict of interest.

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Aceves-Serrano, L., Sossi, V. & Doudet, D.J. Comparison of Invasive and Non-invasive Estimation of [11C]PBR28 Binding in Non-human Primates. Mol Imaging Biol 24, 404–415 (2022). https://doi.org/10.1007/s11307-021-01661-6

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