Positron Emission Tomography Imaging of Cell Trafficking: A Method of Cell Radiolabeling
October 27th, 2023
Presented here is a protocol to radiolabel cells with a positron emission tomography (PET) radioisotope, 89Zr (t1/2 78.4 h), using a ready-to-use radiolabeling synthon, [89Zr]Zr-p-isothiocyanatobenzyl-desferrioxamine ([89Zr]Zr-DBN). Radiolabeling cells with [89Zr]Zr-DBN allows noninvasive tracking and imaging of administered radiolabeled cells in the body with PET for up to 7 days post-administration.
Overview
This protocol describes a stepwise method for radiolabeling cells with zirconium-89-DBN and its non-invasive tracking by PET. This technique provides a reliable method for tracking administered radiolabeled cells in the body for up to 7 days post-administration.
Key Study Components
Area of Science
- Neuroscience
- Cell Therapy
- Imaging Techniques
Background
- Radiolabeling cells allows for tracking and imaging in vivo.
- 89 Zr has a half-life of 78.4 hours, suitable for PET imaging.
- This method aids in understanding pharmacokinetics of cell-based therapies.
- It is particularly useful for neurological diseases and cancers.
Purpose of Study
- To provide a protocol for non-invasive tracking of radiolabeled cells.
- To enhance understanding of cell therapies through imaging.
- To assist new users in adopting radiolabeling techniques.
Methods Used
- Preparation of hydroxamate resin column.
- Activation of the column with anhydrous acetonitrile.
- Covalent conjugation of zirconium-89-DBN to cell surface proteins.
- Stepwise protocol for radiolabeling cells.
Main Results
- Successful radiolabeling of cells with [89 Zr]Zr-DBN.
- Non-invasive tracking of cells using PET imaging.
- Protocol provides troubleshooting guidance for new users.
- Demonstrated stability and reliability of the radiolabeling method.
Conclusions
- The protocol is instrumental for researchers in cell therapies.
- It facilitates the study of pharmacokinetics via PET imaging.
- New users can effectively learn and apply the technique.
Frequently Asked Questions
Executive Industry Relevance
Noninvasive PET imaging of radiolabeled cell therapies enables direct, quantitative tracking of cell trafficking and persistence in vivo, addressing a critical gap in pharmacokinetic and pharmacodynamic understanding. This capability supports predictive confidence in cell therapy development, informing risk-adjusted advancement and portfolio prioritization. The method's compatibility with diverse cell types positions it as a reusable platform for translational and preclinical R&D.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables direct interrogation of cell fate and biodistribution in living systems.
- Supports mechanistic de-risking by clarifying trafficking and retention profiles.
- Facilitates functional validation of engineered or lineage-guided cell products.
- Provides quantitative data to inform go/no-go decisions in cell therapy pipelines.
Screening & Assay Development
- Establishes standardized radiolabeling protocols for reproducible cell tracking assays.
- Delivers quantitative PET readouts for comparative evaluation of cell preparations.
- Supports assay scalability and cross-study comparability through robust radiolabeling chemistry.
- Enables reliable assessment of cell viability and labeling efficiency post-radiolabeling.
Translational & Preclinical Research
- Aligns preclinical cell trafficking data with translational biomarker strategies.
- Provides continuity from discovery through IND-enabling studies by supporting longitudinal cell tracking.
- Reduces biological uncertainty in preclinical models by enabling direct visualization of cell fate.
- Supports risk-adjusted advancement by clarifying in vivo persistence and clearance profiles.
Pipeline & Workflow Integration
This radiolabeling and PET imaging workflow integrates from early discovery through preclinical validation, supporting lead identification and translational continuity for cell-based therapies.
- Discovery Biology: Quantitative PET imaging enables hypothesis testing of cell trafficking and engraftment.
- Screening: Standardized radiolabeling supports reproducible, quantitative cell tracking assays.
- Analytics: PET readouts provide direct, quantitative measurements of cell distribution and retention.
- Translational Research: Enables alignment of preclinical cell fate data with clinical biomarker strategies.
- Enterprise Reuse: The platform is adaptable to multiple cell types and therapeutic modalities.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence and reduces mechanistic ambiguity in cell therapy development.
- Operational Value: Delivers standardized, scalable, and reproducible radiolabeling workflows.
- Strategic Value: Informs better go/no-go decisions and reduces late-stage biological risk.
- Portfolio Impact: Supports risk-adjusted prioritization and advancement of cell therapy candidates.
Implementation Considerations
- Requires expertise in radiochemistry, cell handling, and PET imaging analytics.
- Needs access to radiolabeling infrastructure and PET imaging facilities.
- Demands rigorous cross-team standardization for reproducibility and data comparability.
- Adaptable to a range of cell types but may require optimization for specific products.
- Radiolabeling efficiency and cell viability must be validated for each application.
Biopharma FAQs
Chapters in this video
0:04
Introduction
1:04
Preparation of [89Zr]Zr‐p‐Isothiocyanatobenzyl‐Desferrioxamine ([89Zr]Zr‐DBN)
3:06
Obtaining 89Zr as [89Zr]ZrCl4
5:11
Radiolabeling of Cells
8:24
Results: 89Zr Chelation Efficiency with DFO‐Bn‐NCS, Cell Radiolabeling Efficiency and Stability of Zr‐89 Label on Radiolabeled Cells
9:29
Conclusion
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