Chemistry Reference
In-Depth Information
16
cheMIcal StrateGIeS for the developMent
of MultIModal IMaGInG probeS
uSInG nanopartIcleS
Amanda L. Eckermann, Daniel J. Mastarone and Thomas J. Meade
Departments of Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering and Radiology,
Northwestern University, Evanston, IL, USA
16.1
IntroductIon
The ability to interrogate
in vivo
anatomical features and biochemical processes has stimulated growth in the relatively new
field of molecular imaging. In a sense, molecular imaging is the intersection of classical diagnostic imaging and molecular
biology with the goal of allowing molecular processes to be visualised within a living organism. There are a number of
physical techniques (or modalities) frequently employed in molecular imaging experiments, and each has its own inherent
strengths and weaknesses regarding resolution, sensitivity, and temporal limitations. These techniques include, but are not
limited to, positron emission tomography (PET), single photon emission computed tomography (SPECT), X-ray computed
tomography (CT), magnetic resonance imaging (MRI), 2-photon optical imaging, near-IR fluorescence imaging (NIRFI),
and ultrasound (US).
It has been evident for many years that combining one or more modalities to investigate a problem allows researchers to
capture the strengths of more than one of these techniques. Therefore, the development of instrumentation capable of cou-
pling more than one modality has been achieved (PET-CT-SPECT is an excellent example). Further, in order to differentiate
specific anatomical features, individual cells, and subcellular domains, imaging agents (or probes) are frequently employed.
While molecular multimodal agents exist, the chemistry of combing multiple probes in one molecule, macromolecule, or
supramolecule is complex [1-3]. Nanoparticles are ideal scaffolds for combining two or more imaging modalities. Multiple
moieties may be attached to the nanoparticle surface for amplification while the nanoparticle itself may consist of material
suitable for imaging. This chapter focuses on the most recently reported (2010-2012) nanoparticle agents that have been dem-
onstrated
in vivo.
Wherever possible, we include the details of the chemistry used to assemble the multimodal components.
16.1.1
General chemical Methods
While a variety of bioconjugate techniques for labelling nanoparticles have been developed, we have chosen to focus on the
most widely used. This section describes the general methods of chemical conjugations (Scheme 16.1), silanisation
(Scheme 16.2), and electrostatic adsorption (Figure 16.1). Nanoparticles can be generated with thiol-, carboxylic acid-, or
amine-functionalised surfaces. Peptide coupling is the formation of an amide bond between a carboxylic acid and an amine.
Dyes or other species with carboxylic acids are often pre-activated using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide
(EDC) and N-hydroxyl succinimide (NHS) to form a succinimidyl ester that is more reactive toward the amine than the
acid alone. This approach has been used, for example, to attach Gd(III) chelates to nanodiamonds [4]. Another common
