Fluorescent Macromolecular Sensors of Enzymatic Activity for In Vivo Imaging - Progress in Molecular Biology and Translational Science - page 348

CHAPTER NINE

Fluorescent Macromolecular
Sensors of Enzymatic Activity
for In Vivo Imaging

Alexei A. Bogdanov, Mary L. Mazzanti
Laboratory of Molecular Imaging Probes, Department of Radiology, University of Massachusetts Medical
School, Worcester, Massachusetts, USA

Contents
1. Introduction 350

2. Enzyme Activity and Dysregulation as a Predictor of Disease 350

3. Fluorescence Detection In Vivo 352

4. Principles of Enzymatic Activity Sensors Based on Fluorescence Changes 357

5. Macromolecular Fluorescent Probes 358

6. Pharmacokinetics of PGC and Imaging of Activation 369

7. Applications of Macromolecular Fluorescent Sensors in Cancer Imaging 372

8. Alternative Enzyme-Targeted Strategies in Imaging Cancer 374

9. Macromolecular Sensors in Fluorescent Imaging of Inflammation
and Vascular Disease 377

10. Conclusions 379

References 380

Abstract
Macromolecular imaging probes (or sensors) of enzymatic activity have a unique place
in the armamentarium of modern optical imaging techniques. Such probes were ini-
tially developed by attaching optically “ silent ” fluorophores via enzyme-sensitive linkers
to large copolymers of biocompatible poly(ethylene glycol) and poly(amino acids). In
diseased tissue, where the concentration of enzymes is high, the fluorophores are freed
from the macromolecular carrier and regain their initial ability to fluoresce, thus allowing
in vivo optical localization of the diseased tissue. This chapter describes the design and

application of these probes and their alternatives in various areas of experimental
medicine and gives an overview of currently available techniques that allow imaging
of animals using visible and near-infrared light.