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Whole-body tracking of single cells via positron emission tomography

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In vivo molecular imaging can measure the average kinetics and movement routes of injected cells through the body. However, owing to non-specific accumulation of the contrast agent and its efflux from the cells, most of these imaging methods inaccurately estimate the distribution of the cells. Here, we show that single human breast cancer cells loaded with mesoporous silica nanoparticles concentrating the 68Ga radioisotope and injected into immunodeficient mice can be tracked in real time from the pattern of annihilation photons detected using positron emission tomography, with respect to anatomical landmarks derived from X-ray computed tomography. The cells travelled at an average velocity of 50 mm s−1 and arrested in the lungs 2–3 s after tail-vein injection into the mice, which is consistent with the blood-flow rate. Single-cell tracking could be used to determine the kinetics of cell trafficking and arrest during the earliest phase of the metastatic cascade, the trafficking of immune cells during cancer immunotherapy and the distribution of cells after transplantation.

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Fig. 1: Overview of the CellGPS workflow.
Fig. 2: Cell-labelling method using 68Ga-MSN for sensitive tracking.
Fig. 3: Static PET imaging of small cell populations in mice and ex vivo validation.
Fig. 4: Dynamic PET tracking of single cells.

Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. The raw PET–CT data (list-mode format) are available from the corresponding author on request.

Code availability

The computer codes used to reconstruct cell trajectories from list-mode PET data are provided in the Supplementary Information, and are also available as an online Code Ocean capsule25 at

Change history

  • 25 June 2020

    In the version of this Article originally published, the Reporting Summary was outdated. This has now been replaced and the updated version is available online.


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We thank the following individuals for support and assistance: M. Wardak, C. Azevedo, T. Shaffer, H. Li, F. Habte, A. Natarajan, S.-M. Park, T. Doyle and S. Lee. The ShowVol package by D.-J. Kroon was used for surface rendering. This research was funded in part by the National Institutute of Health grants 5R21HL127900 and T32CA1186810. Experiments were performed at the Stanford small-animal imaging facility, the Stanford radiochemistry facility and the Stanford nano facility.

Author information

Authors and Affiliations



K.O.J. performed in vitro and in vivo experiments. T.J.K. performed physical tests and processed data. J.H.Y. characterized nanoparticles and optimized their radiolabelling. S.R. imaged ex vivo specimens. W.Z. reconstructed CT images. B.H. contributed to the design of the methods. G.P. reconstructed dynamic cell trajectory data. K.O.J. and G.P. designed the study and wrote the manuscript. K.R.-H., S.S.G. and G.P. supervised the study.

Corresponding author

Correspondence to Guillem Pratx.

Ethics declarations

Competing interests

G.P. is listed as inventor on a US patent that covers the algorithm used in this study for cell trajectory reconstruction (no. US9962136B2). The other authors declare no competing interests.

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Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Figs. 1–23 and the captions for Supplementary Videos 1–6.

Reporting Summary

Supplementary Code

Reconstruction of cell trajectories from list-mode PET data.

Supplementary Video 1

Cell position (red dot) reconstructed from list-mode PET data over time. A single cell (67 Bq) was flown, moving through a length of plastic tubing coiled around a 3D printed cylinder.

Supplementary Video 2

Cell position (red dot) reconstructed from list-mode PET data over time. A single cell (27 Bq) was injected into the forepaw of a mouse.

Supplementary Video 3

Cell position (red dot) reconstructed from list-mode PET data over time. A single cell (30 Bq) was injected into the tail vein of a mouse.

Supplementary Video 4

Cell position (red dot) reconstructed from list-mode PET data over time. A single cell (70 Bq) was injected into the tail vein of a mouse through a catheter, while PET data were acquired.

Supplementary Video 5

Cell position (red dot) reconstructed from list-mode PET data over time. A single cell (70 Bq) was injected into the tail vein of a mouse through a catheter, while PET data were acquired.

Supplementary Video 6

Cell position (red dot) reconstructed from list-mode PET data over time. A single cell (70 Bq) was injected into the tail vein of a mouse through a catheter, then the organs were excised and imaged using PET–CT.

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Jung, K.O., Kim, T.J., Yu, J.H. et al. Whole-body tracking of single cells via positron emission tomography. Nat Biomed Eng 4, 835–844 (2020).

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