Contrast Media & Molecular Imaging

Animal studies have during the last years revealed a great potential for molecular imaging with different types of targeting molecules. Challenges of bringing such agents into common clinical use are discussed, with a special focus on the challenges to image intracellular targets following intravenous injection of the agents.

The USPIO nanoparticles surface is modified with mPPDA-silane and then conjugated with RGD. The in vitro and in vivo MR imaging studies are performed to evaluate targeting specificity and to differentiate the expression level of integrin receptor. This result implices that the RGD nanoparticles, which greatly enhance the MR imaging, are sufficiently sensitive to detect a tumor at an early stage.

CEST signal of EuDOTA–(gly)₄− is quenched upon conjugation to the surface of silica nanoparticles partially due to rapid prototropic exchange catalyzed by charged groups on the nanoparticle surface.

A PARACEST MRI contrast agent, Yb–DO3A–oAA, has two CEST effects that are dependent on pH. A ratio derived from these CEST effects can accurately and precisely measure pH in a manner that is independent of concentration, T₁ relaxation time, and incomplete saturation.

We used self-synthesied pvp-SPIO to label beta-cell line or islets. We observed our PVP-SPIO displayed good biocompatibility and magnetic properties, and possessed superior labeling efficiency than Feridex. There existed correlation between the number of labeled cells and R2 value on MRI. The signal intensity and the intracellular iron content also well correlated with the viability of labeled cells. The signal intensity on MRI might be useful predictor to evaluate the number and the viability of labeled cells.

Three-dimensional Overhauser-enhanced MRI (OMRI) of a free radical injected in glioma-bearing mice was performed at a constant field of 0.194 T. Images were acquired within 5 min without significant animal overheating. Signal amplifications ranged from 2 in tumors to 10 in brain arteries. Time-course of signal enhancement could be measured by 2D OMRI at 15 s time intervals. The method opens the way for molecular imaging of biological activities able to generate OMRI-visible free radicals.

Color map of signal enhancement in a selected slice of a 3D image of mouse brain.

Human pancreatic cancer cells labeled with SPIO were inoculated into nude mice to induce tumor xenograft and MR imaging performed with a 1.5 T MR scanner at the first, second and third week after the inoculation. The tumor xenograft showed significant center and peripheral signal intensity patterns on MR imaging, which derived from the heterogeneous distribution of iron following the time of inoculation. This would indicate that MR imaging may monitor the development of the tumor.

The fluorophore-normalized fluorescence, quantum yields and fluorescence lifetimes of rhodamine B-containing fluorescent magnetoliposomes (FLU-ML) were substantially reduced by inner filter effects as the magnetoliposome concentration was increased, by increasing molar rhodamine B fraction, and by quenching originating from the iron oxide cores. However, the internalized FLU-ML in human prostata carcinoma cells were clearly visible by fluorescence microscopy. At the FLU-ML concentrations used (up to 3 × 10⁻³ M Fe), cell viability was not substantially impaired.

We propose a multimodal radiolabeled paramagnetic liposomal contrast agent for simultaneous imaging with SPECT and MRI. As SPECT-based quantification allows determination of the gadolinium concentration, the MRI signal can be deconvoluted to derive the net contrast agent relaxivity. The latter provides indirect information about the intracellular location of the multimodal nanoparticle as a reduced relaxivity indicates compartmentalization into cell organelles (i.e. endosomes).

A challenge with cardiac cell therapy is determining the location of cells relative to the region of reduced perfusion in the myocardium. We have developed a novel imaging technique by sequentially acquiring ¹¹¹In-labeled cell information and first-pass perfusion CT information using the Siemens Symbia-T6 SPECT/CT system to obtain a single fused image displaying both sets of information. We have shown that this is an effective hybrid platform for the localization of cells in relation to the area of reduced perfusion.

Hyperpolarized ¹³C-MRS can potentially become a powerful tool to study the physiology of organs such as the heart, through the quantification of kinetic patterns under pathophysiological conditions. In this study we assessed myocardial uptake and metabolism of hyperpolarized [1-¹³C]pyruvate in anesthetized pigs during dobutamine-induced stimulation. We detected an increase of the apparent kinetic constants for bicarbonate and lactate of two fold during dobutamine infusion: these data parallel with the Rate Pressure Product, an indirect parameter of cardiac oxygen consumption.

Hexadentate 1,4,7-triazacyclonane (TACN) capped Gd-hydroxypyridinone (HOPO) complexes with 2 or 3 sites open for water coordination have been synthesized. These complexes have been conjugated via peptide bond formation to a 40 kDa degradable esteramide (EA) dendrimer to increase relaxivity (to r₁ = 31 mM^-1s^-1, r₂ = 52 mM^-1s^-1 at 60 MHz and 37 °C), solubility, and biocompatibility.