Page 19 - TPIS2022

Lecture title:
Multi-modality Molecular Imaging in Preclinical Models of

Disease (Cancer/Infection)

ABSTRACT:
Molecular Imaging is the noninvasive, real-time visualization of biochemical events at the
cellular and molecular level within living cells, tissues and subjects. Over the years, many imaging
methods or modalities have been developed. These modalities can span the electromagnetic
spectrum from gamma rays to radio-waves. Different approaches possess different imaging
properties. For instance, optical imaging (bioluminescence and fluorescence) is known for
its ease of use; Positron Emission Tomography (PET) is known for its sensitivity while
Magnetic Resonance Imaging (MRI) or Computer Tomography (CT) can yield high resolution
anatomical detail. Oftentimes, modalities with complementary properties will be combined.
In this talk, we will give examples of such multi-modality studies in preclinical (i.e. animal)
models of disease. We will start off with some studies in bioluminescent imaging.
Bioluminescence is the biochemical emission of light by living organisms such as fireflies and
deep-sea organisms. Biomolecules with these electromagnetic manifestations can be exploited
to study the behavior and etiology of both normal and diseased tissue. One prominent
disease is Glioblastoma (GBM) which is the most common yet most lethal of primary brain
cancers with a one-year post-diagnosis survival rate of 65% and a five-year survival rate of
barely 5%. Patient-derived glioblastoma cell lines can be isolated and then genetically
modified such that they can express a reporter gene such as Firefly or Renilla Luciferase (fLuc
or rLuc respectively) thus giving one the opportunity to track tumor burden in preclinical
models of GBM xenografts via Bioluminescent and/or Fluorescent imaging. But, this
imaging approach is translationally unfeasible as it involves genetic modification of target
tissue (e.g. cancer cells) that may be hard to isolate totally and clinically. This talk will also
present examples of proof of concept studies in which we validate PET and MRI imaging
approaches through preclinical models of luciferase expressing cancer or infectious tissues.
We will also show an example of a study in which anatomical information on cancer cells
(as visualized by T2*-weighted MRI) is complemented by molecular information as
visualized by a PET tracer for metabolic activity ([18F]-DASA). Finally, we will give an example
of how loss of tumor burden via immunotherapy in a preclinical model of GBM that has
a luciferase-expressing xenograft, can be compared and connected to immunoimaging of
therapeutic Chimeric Antigen Receptor (CAR) T-cells (i.e. T-lymphocyte immune cells) via
MRI, i.e. a clinically translatable modality that can track the progress of immune cells into
target diseased tissue. In summary, these studies show how one can use different modalities
to either validate the interpretation of a molecular image or to yield complementary
anatomical versus molecular (and metabolic) imaging information or to follow two different
tissue compartments in the same location. Ultimately such studies will yield insights into the
most translatable, and clinically-focused imaging approaches.

5 International TPCF Preclinical Imaging Symposium (2022) 19
th