Biomedical Engineering Reference
In-Depth Information
SPION formulation (VSOPC184) has also generated first pass images that are
equivalent to those taken using Gd based agents.
259
The results of the Phase I
clinical trials have demonstrated acceptable safety, tolerability, and data that
exhibited efficacy.
260
The NMs that are being evaluated as MRA agents have
long half-life in the plasma making them suitable for detection of small vessels
with slow and/or complex flow; and may be able to advance angiography as an
imaging tool for personalized medicine.
261
The potential applications of these
NMs as MRA agents that are being tested in humans and/or animals include
functional imaging,
262
perfusion imaging,
263
dynamic detection of bleeding,
264
and the characterization of tumor related angiogenesis.
265
The first molecular specific NM based contrast agent binds to HER2, a
growth factor whose overexpression is associated with more aggressive and
malignant breast cancer phenotypes.
266,267
This NMs-based contrast agent is
an engineered compact three-helix bundle (i.e. affibody
®
) that entered Phase I
clinical trials in August 2009 when AffibodyAG obtained the final approval and
funding for a Phase I study of its ABY025 compound.
3
Results from a Phase 1
first-in-human clinical trial in seven HER2-positive or -negative females with
metastasized breast cancer, assessing safety of use, tissue distribution of ABY-
025 and possibilities to discriminate low/high HER2- expression in lesions.
268
The results gave excellent quality SPECT images and full body scans that were
recorded and analyzed for tissue distribution. Evidence for differences in uptake
and kinetics between low/high HER2-expressing lesions were reported. There
were no observed drug induced adverse reactions and no induced formation of
antibodies against ABY-025. Their results indicated that ABY-025 can be used
safely in humans for whole body HER2-receptor molecular imaging capabili-
ties as noted with a previous generation Affibody molecule. These clinical trial
results provided promising indications of in vivo HER2-receptor status assess-
ment capabilities and the potential to guide treatment in cancer patients.
268
7.6.2 NMs as Imaging Contrast Agents in Preclinical
Development
The success in human applications of the NMs-based imaging contrast agents
has spurred the upsurge in the development of more efficient and complex
nanoparticle systems. The NIH Molecular Imaging and Contrast Agent Data-
base (MICAD) reveals over 50 nanoparticle-based systems that are currently
undergoing preclinical development.
269
A few of these NMs are shown in
Table 7.4
.
Some of these NMs are being used for in vitro studies. Mesenchymal
stem cells (MSCs), were labeled with commercially available FluidMAG iron
nanoparticles.
270
FluidMAG nanoparticles are ferrofluids consisting of an aque-
ous dispersion of magnetic IOs that have hydrodynamic diameter of 200 nm
and a starch coating. Loebinger, et al. showed that the FlluidMag labeled cells
retained their MSC characteristics and the ability to differentiate into stromal
