Historical Perspective on Nanoparticles in Imaging from 1895 to 2000 - Nanotechnology for Biomedical Imaging and Diagnostics - page 10

finally demonstrated tissue specificity for targeting liposomes [27-29]. One of the
outcomes of this study was the recognition and the rise of a variety of 111 In-labeled
nanoparticles for SPecT imaging [30-33].

1.5 magnetic imaging witH nanoParticles (1980s-2000)

1.5.1 mri nanoparticles with Paramagnetic ions

clinical applications of MrI in the beginning of the 1980s, initiated by the first com-
mercially available MrI scanners from general electric, opened a new era in
imaging. The fascinating early history of MrI contrast agents has been well docu-
mented, and the reader is encouraged to review the reference [34]. In MrI, a strong
magnetic field pulse is applied to a body causing certain atoms, such as protons, to
be excited. The rate of the following relaxation is recorded and transferred into an
image. This concept of relaxation came from nuclear magnetic resonance (NMr),
the predecessor of today's MrI, as a method for characterizing organic compounds.
By the middle of the 1970s, chemists recognized that beside three major NMr
parameters, chemical shifts, coupling constants, and integrated areas, there were two
more parameters, namely, spin relaxation time ( T 1 ) and lattice relaxation time ( T 2 ),
that could be used to characterize the structure of the organic molecule [35]. Hence,
there were also a number of ways whereby spin-lattice relaxation times could be
chemically manipulated. among them was the use of paramagnetic metal ions
including gadolinium (gd) that affected the relaxation times of associated ligands
and nearby solvent molecules. Not surprisingly, the first MrI contrast agents
described in the early 1980s were based on gd complexes.
To enhance the Mr signal, metal atoms should be freely exposed to biological
water. This requirement demands the location of the metal at the exterior of the
nanoparticle. To address this problem, g. Kabalka from the University of Tennessee
in 1987 prepared gd complexes with DTPa carrying two lipophilic long chains that
were integrated into the lamellar phase of liposome particles [36] (fig. 1.8). This
proof-of-concept approach showed that the relaxation rate in the liver, post ex vivo ,
increased by 180%. Other metal complexes such as Mn 2+ complexes have been also
explored. The early attempts to entrap Mn 2+ -DTPa in multilamellar liposomes [37]
were not entirely successful; the complex from nanoparticles leaked out although the
image showed the difference in contrast agent biodistribution compared to the free
complex. In a parallel effort, the group of g. Navon from Tel-aviv University added
serum albumin to stabilize the complex inside the liposome and enhance their effect
on water proton relaxation rates [38]. However, these promising in vitro results were
not followed by imaging in vivo .

1.5.2 supermagnetic nanoparticles

The breakthrough in the development of MrI contrast agents began from the intro-
duction of supermagnetic nanoparticles in the mid-1980s. In contrast to by that time
popular T 1 gd paramagnetic agents, this class of contrast agents gave rise to a dramatic