Quantitative In Vivo Imaging for IND-Enabling Programs

Executive Summary

Successful cell therapy development requires definitive, noninvasive methods to track cell engraftment, persistence, and biodistribution in vivo. This asset outlines the application of advanced imaging modalities, including Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI), to provide quantitative data for preclinical programs. These techniques offer direct visualization of cell fate, informing dose selection and providing substantive data for regulatory submissions to global bodies like the FDA, EMA, and Germany’s Paul-Ehrlich-Institut (PEI). By adapting principles from other advanced therapeutic fields, we design tailored imaging strategies that minimize clinical risk.

Frequently Asked Questions

Q: How can in vivo imaging de-risk a CAR-T or stem cell therapy program before clinical trials?

In vivo imaging provides direct, longitudinal evidence of cell engraftment, proliferation, and non-target tissue biodistribution. This data is invaluable for establishing a clear relationship between dose, exposure, and biological activity, which strengthens the rationale for clinical starting dose and satisfies a key requirement for IND-enabling toxicology studies.

Q: What are the primary differences between using PET and MRI for tracking cell therapy products?

PET offers high sensitivity for detecting radiolabeled cells or reporter gene expression, making it ideal for quantitative tracking of cell viability and expansion. MRI provides superior anatomical context and high spatial resolution, which is useful for visualizing cell localization within specific tissues or tumors, often using iron oxide nanoparticles as contrast agents. The choice depends on the specific biological questions of the program.

Q: How does Franklin Biolabs ensure its animal models are appropriate for cell therapy imaging studies?

We develop customized animal models with immune systems selected to mirror the human response, which is a foundational step for interpreting engraftment data. Just as screening for pre-existing neutralizing antibodies is a known variable in viral vector programs (PMID: 26067568), understanding the immunological baseline of the host system is a prerequisite for obtaining meaningful cell therapy persistence data.

Noninvasive Monitoring of Somatic Cell Therapy Engraftment

The therapeutic success of cell-based modalities : including CAR-T, TCR-T, and iPSC-derived therapies : depends on their ability to engraft, persist, and function within the target tissue. Traditional terminal endpoint analyses, such as histology, provide only a single snapshot in time. Advanced in vivo imaging techniques offer a longitudinal, quantitative alternative to assess the pharmacokinetics and pharmacodynamics of these complex therapies.

This approach allows for the direct visualization of cellular activity over the entire course of a preclinical study within the same animal, reducing animal usage and generating more robust datasets. Our >100,000 sq ft facility is equipped to handle these complex study designs.

Adapting Reporter Gene Strategies for Cellular Tracking

The core principle of using reporter genes for noninvasive tracking can be effectively adapted for cell therapies. Methodologies established for quantifying in vivo gene transfer with viral vectors provide a strong technical precedent (PMID: 12639305).

By engineering therapeutic cells (e.g., CAR-T or MSCs) to express a reporter protein detectable by PET or Single-Photon Emission Computed Tomography (SPECT), we can achieve several objectives:

• Quantify the magnitude and duration of cell engraftment at the target site.

• Monitor cell proliferation or contraction over time.

• Assess non-target tissue biodistribution to build a comprehensive safety profile.

Selecting the Appropriate Imaging Modality

The selection of an imaging platform is tailored to the specific therapeutic asset and the biological questions being addressed. No single technique is universally superior; instead, a data-driven strategy dictates the best approach.

Modality	Primary Application	Resolution	Key Considerations
PET / SPECT	High-sensitivity quantitative tracking of cell viability and expansion.	Lower Spatial	Requires radiolabeling of cells or use of a reporter gene construct.
MRI	High-resolution anatomical localization of cell populations.	High Spatial	Often requires labeling cells with a contrast agent (e.g., SPIO nanoparticles).
Bioluminescence (BLI)	High-throughput screening in early, non-GLP discovery phases.	Low Spatial	Limited tissue penetration; best suited for superficial targets in small animals.

Our scientific teams design and execute these studies to align with harmonized international guidelines (ICH), supporting multi-jurisdictional IND and Investigational Medicinal Product Dossier (IMPD) submissions to bodies like the FDA and Germany’s Paul-Ehrlich-Institut (PEI). This approach was central to our collaboration with leading industry partners. It is built upon the track record of our core scientific leadership, whose work prior to our 2024 launch achieved a 100% successful IND rate since 2019 and established the 18-24 month timeline to move candidates into the clinic. The ethical stewardship of these models is a core operational focus, and we are committed to the 3Rs principles of animal research.

This work is a component of our broader capabilities detailed in our Preclinical | Translational Services offerings.

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