26 research outputs found
Gd Complexes of DO3A-(Biphenyl-2,2′-bisamides) Conjugates as MRI Blood-Pool Contrast Agents
We report the synthesis of DO3A derivatives of 2,2′-diaminobiphenyl
(<b>1a</b>,<b>b</b>) and their Gd complexes of the type
[Gd(<b>1</b>)(H<sub>2</sub>O)]·<i>x</i>H<sub>2</sub>O (<b>2a</b>,<b>b</b>) for use as new MRI blood-pool
contrast agents (BPCAs) that provide strong and prolonged vascular
enhancement. Pharmacokinetic inertness of <b>2</b> compares
well with that of structurally related Dotarem, a DOTA-based MRI CA
currently in use. The <i>R</i><sub>1</sub> relaxivity in
water reaches 7.3 mM<sup>–1</sup> s<sup>–1</sup>, which
is approximately twice as high as that of Dotarem (<i>R</i><sub>1</sub> = 3.9 mM<sup>–1</sup> s<sup>–1</sup>).
They show interaction with HSA to give association constants (<i>K</i><sub>a</sub>) in the order of two (∼10<sup>2</sup>), revealing the existence of the blood-pool effect. The in vivo
MR images of mice obtained with <b>2</b> are coherent, showing
strong signal enhancement in both heart, abdominal aorta, and small
vessels. Furthermore, the brain tumor is vividly enhanced for an extended
period of time
Surface Design of Eu-Doped Iron Oxide Nanoparticles for Tuning the Magnetic Relaxivity
Relaxivity
tuning of nanomaterials with the intrinsic <i>T</i><sub>1</sub>–<i>T</i><sub>2</sub> dual-contrast
ability has great potential for MRI applications. Until now, the relaxivity
tuning of T<sub>1</sub> and T<sub>2</sub> dual-modal MRI nanoprobes
has been accomplished through the dopant, size, and morphology of
the nanoprobes, leaving room for bioapplications. However, a surface
engineering method for the relaxivity tuning was seldom reported.
Here, we report the novel relaxivity tuning method based on the surface
engineering of dual-mode <i>T</i><sub>1</sub>–<i>T</i><sub>2</sub> MRI nanoprobes (DMNPs), along with protein
interaction monitoring with the DMNPs as a potential biosensor application.
Core nanoparticles (NPs) of europium-doped iron oxide (EuIO) are prepared
by a thermal decomposition method. As surface materials, citrate (Cit),
alendronate (Ale), and poly(maleic anhydride-<i>alt</i>-1-octadecene)/poly(ethylene
glycol) (PP) are employed for the relaxivity tuning of the NPs based
on surface engineering, resulting in EuIO-Cit, EuIO-Ale, and EuIO-PP,
respectively. The key achievement of the current study is that the
surface materials of the DMNP have significant impacts on the <i>r</i><sub>1</sub> and <i>r</i><sub>2</sub> relaxivities.
The correlation between the hydrophobicity of the surface material
and longitudinal relaxivity (<i>r</i><sub>1</sub>) of EuIO
NPs presents an exponential decay feature. The <i>r</i><sub>1</sub> relaxivity of EuIO-Cit is 13.2-fold higher than that of EuIO-PP.
EuIO can act as <i>T</i><sub>1</sub>–<i>T</i><sub>2</sub> dual-modal (EuIO-Cit) or <i>T</i><sub>2</sub>-dominated MRI contrast agents (EuIO-PP) depending on the surface
engineering. The feasibility of using the resulting nanosystem as
a sensor for environmental changes, such as albumin interaction, was
also explored. The albumin interaction on the DMNP shows both <i>T</i><sub>1</sub> and <i>T</i><sub>2</sub> relaxation
time changes as mutually confirmative information. The relaxivity
tuning approach based on the surface engineering may provide an insightful
strategy for bioapplications of DMNPs and give a fresh impetus for
the development of novel stimuli-responsive MRI nanoplatforms with <i>T</i><sub>1</sub> and <i>T</i><sub>2</sub> dual-modality
for various biomedical applications
Heteronuclear Gd-<sup>99m</sup>Tc Complex of DTPA-Bis(histidylamide) Conjugate as a Bimodal MR/SPECT Imaging Probe
The work describes the synthesis and in vivo application
of heterotrimetallic
complexes of the type {Gd(H<sub>2</sub>O)[(M(H<sub>2</sub>O)(CO)<sub>3</sub>)<sub>2</sub>(<b>1</b>)]} {<b>1</b> = DTPA-bis(histidyl-amide); <i>M</i> = Re (<b>3a</b>); <sup>99m</sup>Tc (<b>3b</b>)} for dual modality MR/SPECT imaging. Here, the DTPA-bis(histidylamide)
conjugate functions as a trinucleating chelate incorporating Gd in
the DTPA core with Re or <sup>99m</sup>Tc in the pair of histidylamide
side arms. The two complexes are chemically equivalent as revealed
by HPLC, and their “cocktail mixture” (<b>3a</b> + <b>3b</b>) has demonstrated itself to be essentially a single
bimodal imaging probe. The present system has thus overcome the sensitivity
difference problem between MRI and SPECT and paved the way for practical
applications
Manganese Complex of Ethylenediaminetetraacetic Acid (EDTA)–Benzothiazole Aniline (BTA) Conjugate as a Potential Liver-Targeting MRI Contrast Agent
A novel manganese(II) complex based
on an ethylenediaminetetraacetic
acid (EDTA) coordination cage bearing a benzothiazole aniline (BTA)
moiety (Mn-EDTA-BTA) was designed and synthesized for use as a liver-specific
MRI contrast agent with high chelation stability. In addition to forming
a hydrophilic, stable complex with Mn<sup>2+</sup>, this new Mn chelate
was rapidly taken up by liver hepatocytes and excreted by the kidneys
and biliary system. The kinetic inertness and <i>R</i><sub>1</sub> relaxivity of the complex were much higher than those of
mangafodipir trisodium (MnDPDP), a clinically approved liver-specific
MRI contrast agent. The diagnostic utility of this new Mn complex
in MRI was demonstrated by high-sensitivity tumor detection in an
animal model of liver cancer
Gadolinium Complex of <sup>125</sup>I/<sup>127</sup>I‑RGD-DOTA Conjugate as a Tumor-Targeting SPECT/MR Bimodal Imaging Probe
The work describes the synthesis and in vivo application
of [Gd(L)(H<sub>2</sub>O)]·<i>x</i>H<sub>2</sub>O,
where L is a (<sup>125</sup>I/<sup>127</sup>I-RGD)- DOTA conjugate,
as a tumor-targeting SPECT/MR bimodal imaging probe. Here, (<sup>125</sup>I/<sup>127</sup>I-RGD)-DOTA signifies a “cocktail mixture”
of radioisotopic (<b>1a</b>, L = <sup>125</sup>I-RGD-DOTA) and
natural (<b>1b</b>, L = <sup>127</sup>I-RGD-DOTA) Gd complexes.
The two complexes are chemically equivalent as revealed by HPLC, and
their cocktail mixture exhibits the integrin-specific tumor enhancement,
demonstrating that they constitute essentially a single bimodal imaging
probe. Employment of a cocktail mixture thus proves to be a sole and
practical approach to overcome the sensitivity difference problem
between MRI and SPECT
Gadolinium Complex of 1,4,7,10-Tetraazacyclododecane-1,4,7-trisacetic Acid (DO3A)–Ethoxybenzyl (EOB) Conjugate as a New Macrocyclic Hepatobiliary MRI Contrast Agent
We report the synthesis of a macrocyclic
Gd chelate based on a 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic
acid (DO3A) coordinationn cage bearing an ethoxybenzyl (EOB) moiety
and discuss its use as a <i>T</i><sub>1</sub> hepatobiliary
magnetic resonance imaging (MRI) contrast agent. The new macrocyclic
liver agent shows high chelation stability and high <i>r</i><sub>1</sub> relaxivity compared with linear-type Gd chelates, which
are the current clinically approved liver agents. Our macrocyclic,
liver-specific Gd chelate was evaluated in vivo through biodistribution
analysis and liver MRI, which demonstrated its high tumor detection
sensitivity and suggested that the new Gd complex is a promising contrast
agent for liver cancer imaging
Vivid Tumor Imaging Utilizing Liposome-Carried Bimodal Radiotracer
By
developing a new bimodal radioactive tracer that emits both
luminescence and nuclear signals, a trimodal liposome for optical,
nuclear, and magnetic resonance imaging is efficiently prepared. Fast
clearance of the radiotracer from reticuloendothelial systems enables
vivid tumor imaging with minimum background
Radiometallic Complexes of DO3A-Benzothiazole Aniline for Nuclear Medicine Theranostics
To
develop a radioactive metal complex platform for tumor theranostics,
we introduced three radiopharmaceutical derivatives of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic
acid-benzothiazole aniline (DO3A-BTA, L1) labeled with medical radioisotopes
for diagnosis (<sup>68</sup>Ga/<sup>64</sup>Cu) and therapy (<sup>177</sup>Lu). The tumor-targeting ability of these complexes was
demonstrated in a cellular uptake experiment, in which <sup>177</sup>Lu-L1 exhibited markedly higher uptake in HeLa cells than the <sup>177</sup>Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid
complex. According to in vivo positron emission tomography imaging,
high accumulation of <sup>68</sup>Ga-L1 and <sup>64</sup>Cu-L1 was
clearly visualized in the tumor site, while <sup>177</sup>Lu-L1 showed
therapeutic efficacy in therapy experiments. Consequently, this molecular
platform represents a useful approach in nuclear medicine toward tumor-theranostic
radiopharmaceuticals when <sup>68</sup>Ga-L1 or <sup>64</sup>Cu-L1
is used for diagnosis, <sup>177</sup>Lu-L1 is used for therapy, or
two of the compounds are used in conjunction with each other
High in Vivo Stability of <sup>64</sup>Cu-Labeled Cross-Bridged Chelators Is a Crucial Factor in Improved Tumor Imaging of RGD Peptide Conjugates
Although the importance of bifunctional
chelators (BFCs) is well
recognized, the chemophysical parameters of chelators that govern
the biological behavior of the corresponding bioconjugates have not
been clearly elucidated. Here, five BFCs closely related in structure
were conjugated with a cyclic RGD peptide and radiolabeled with Cu-64
ions. Various biophysical and chemical properties of the Cu(II) complexes
were analyzed with the aim of identifying correlations between individual
factors and the biological behavior of the conjugates. Tumor uptake
and body clearance of the <sup>64</sup>Cu-labeled bioconjugates were
directly compared by animal PET imaging in animal models, which was
further supported by biodistribution studies. Conjugates containing
propylene cross-bridged chelators showed higher tumor uptake, while
a closely related ethylene cross-bridged analogue exhibited rapid
body clearance. High in vivo stability of the copper–chelator
complex was strongly correlated with high tumor uptake, while the
overall lipophilicity of the bioconjugate affected both tumor uptake
and body clearance
Demographic and clinical information for fibromyalgia and control groups.
<p>FIQ, Fibromyalgia impact questionnaire; BFI, Brief fatigue inventory; BDI, Beck depression inventory; BAI, Beck anxiety inventory; IQ, Intelligence quotient.</p