I. Introduction 60

II. SPECT Imaging 60

A. Principles of SPECT Imaging 60

B. Radionuclides Used in SPECT Imaging 62

III. PET Imaging 64

A. Principles of PET Imaging 64

B. Radionuclides Used in PET Imaging 66

IV. SPECT Imaging vs. PET Imaging 67

V. Applications of PET and SPECT Molecular Imaging 69

A. Imaging of RNA 69

B. Imaging of Endogenous Proteins and

Protein Function 71

Imaging of Intracellular Proteins 71

Imaging of Transmembrane Proteins 72

C. Imaging of Exogenous Marker Genes 76

Herpes Simplex Virus-1 Thymidine Kinase 77

Sodium Iodide Symporter 78

Somatostatin Receptor Subtype 2 79

Dopamine-2 Receptor 80

VI. Summary 80

Acknowledgments 80

References 81

I. Introduction

With the development of new molecular imaging probes, sophisticated animal

models, and small-animal imaging devices as well as advances in molecular

biology techniques, molecular imaging has become increasingly important for

understanding basic biological processes in living subjects. Molecular imaging

can be defined as the characterization of biological processes at the cellular

and molecular levels in living animals or humans using remote imaging detectors

(1). This can differ from “classical” diagnostic imaging that focuses on imaging

the end result of these biological processes (2). Molecular imaging modalities

include nuclear imaging, optical imaging, magnetic resonance imaging (MRI),

computed tomography (CT), and ultrasound. All of these modalities offer differ-

ent advantages and limitations for molecular imaging. Most of these advanta-

ges and limitations are centered on issues of spatial and temporal resolution,

sensitivity, molecular probe availability, image acquisition and analysis time,

and cost. The focus of this chapter will be on nuclear imaging, in particular

single photon emission computed tomography (SPECT) and positron emission

tomography (PET). These techniques have the advantages of having a high

sensitivity, being extremely quantitative, and having a number of probes

readily available. They are, however, relatively expensive, expose the subject

to radiation, and have lower spatial resolution than some of the other imaging

modalities. This chapter will describe the basics of SPECT and PET imaging,

describe the advantages and disadvantages of each modality, and give examples

of how each platform is used for molecular imaging applications.