TABLE 1.

Summary Table of Methods for Tracking MSC Tumor Migration

Method	Catergory	Cellular Modification	Contrast Agents	Detection Method	Strengths	Weaknesses	Assessment of Cell Function	References
MRI	Real-time Non- Optical	Magnetic nanoparticles added to cells or coupled to ligands, stable transduction for expression of enzymes or proteins that produce unique MRI signatures.	SPIOs, internalized iron, metal chelates, etc.	Magnetic fields align magnetic moments of atoms; radio frequency fields alter moments and cause atom-specific rotating magnetic fields.	Specific labeling possible based on ligand- expression, clinically used, high sensitivity, fullcontrast agents complicate signal interpretation, expensive tissue penetration, full body analysis, easy cell labeling, safe for multiple uses over time, better spatial resolution than SPECT or PET.	Image lost in contrast artifacts or upon cell division, discarded detection technology, cytotoxicity of certain labeling agents.	No	41, 44, 47
SPECT	Real-time Non- Optical	Uptake of radioisotope labels.	Gamma-emitting radioisotopes (radionuclides).	Tracer emits gamma radiation that is measured directly.	3-D imaging, less expensive than PET, longer- lived more easily-obtained radioisotopes vs PET (Ex: indium-111, 2.8 day halflife, ), gives anatomical and physiological data, better labeling efficiency than PET, used to trace human cells clinically.	Lower resolution than PET (1 cm), drawbacks with stability and imaging time, suboptimal photon energies (depending on tracer), not good for longitudinal studies or multiple uses over time.	Maybe	47, 60
PET	Real-time Non- Optical	Viral modification (ex: Herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk ) (tk ) or other a PET reporter gene) or uptake of radioisotope labels.	Positron-emitting radionuclides.	Pairs of gamma rays detected represent collisions of positrons (emitted by a positron-emitting radionuclides) and electrons within patient at site of tracker.	Clinically used to track human cells, full body analysis, high sensitivity, higher resolution and more current reporter genes than SPECT.	Radiation exposure, costly equipment, genetic modifications of MSCs required, short biological and chemical half-lives of contrast reagents(ex: F-18 FDG, 110 minute halflife), not stable for multiple uses over time, more complex probe construction (tight quality control, advanced chemistry) vs SPECT, can only detect 1 probe (vs SPECT which can detect multiple), needs active uptake (vs SPECT reagents that can diffuse into cells).	Yes	6, 12, 50
Fluorescent gene- Live imaging	Real-time Optical	GFP/other marker transduction.	Fluorescence from fluorescent proteins.	Excitation with specific wavelengths excite molecules to high energy state, relaxation releases photons.	In animal models: excellent for longitudinal studies and imaging different cell types.	Need immunocompatible//FDA-approved fluorescent protein expression for clinical use, high signal attentuationin vivo , not clinically useful, low sensitivity.	Yes	9, 23, 30
Fluorescent dye- Live imaging	Real-time Optical	Fluorescent dye labeling of membrane	Fluorescence from fluorescent dyes.	Excitation with specific wavelengths excite molecules to high energy state, relaxation releases photons.	In animal models: excellent for longitudinal studies and imaging different cell types.	Need immunocompatible/FDA-approved dyes for clinical use, high signal attentuation in vivo , not clinically useful, low sensitivity.	Yes	8, 11
BLI-Live imaging	Real-time Optical	Luciferase transduction.	Bioluminescence from luciferase/luciferin reaction.	Whole animal bioluminescence detection unit quantifies emitted photons from luciferase-labeled cells.	In animal models: excellent for longitudinal studies and imaging different cell types.	Need immunocompatible luciferase expression for clinical use, rapid signal attentuation in vivo , not clinically useful, variable sensitivity.	Yes	10, 13, 38, 63

Abbreviations: MSCs (Mesenchymal Stem Cells), NMRI (Nuclear Magnetic Resonance Imaging), SPIO (Superparamagnetic Iron Oxide), SPECT (Single Photon Emission Computed Tomography) PET (Positron Emission Tomography), 3-D (Three-Dimensional), GFP (Green Fluorescent Protein), BLI (Bioluminescent Imaging)