Contrast-enhanced MRI of murine sponge model for progressive angiogenesis assessed with gadoteridol (ProHance) and gadocoletic acid trisodium salt (B22956/1).

PURPOSE: To investigate the potential value of MRI for noninvasive assessment of angiogenesis in a murine model exploiting the properties of two contrast agents, gadoteridol (ProHance) and gadocoletic acid trisodium salt (B22956/1). MATERIALS AND METHODS: Biocompatible sponges were implanted in both mice flanks. Stimulated sponges contained human recombinant basic fibroblast growth factor (bFGF) as the angiogenic agent; control sponges contained vehicle. Angiogenesis was evaluated by MRI after injection of extravascular (ProHance) or blood-pool (B22956/1) contrast agents at different times after sponge implantation. Sponges signal intensity enhancement was calculated both as the relative enhancement and the rate of relative enhancement. Results from MRI were validated by classic biochemical (hemoglobin level and protein content) and morphological (histology) assays. RESULTS: The intrinsic different properties of ProHance and B22956/1 in wash-in and wash-out kinetics were useful to detect progressive vascularization and the establishment of a functional vascular network in the implants. Moreover, MRI allowed the appreciation of differences in neovessel colonization between bFGF-treated sponges and controls. Hemoglobin level, protein content, and histology confirmed the sponge vascularization and MRI results. CONCLUSION: Contrast-enhanced MRI is a reliable tool to study vascular characteristics in animal models of angiogenesis. The different kinetic properties of contrast agents can provide evidence of different functional neovascularization aspects and levels.

Effect of tamoxifen in an experimental model of breast tumor studied by dynamic contrast-enhanced magnetic resonance imaging and different contrast agents.

OBJECTIVES: The aim of this study was to compare the efficacy of gadoteridol, B22956/1 (a new protein binding blood pool contrast agent), and (Gd-DTPA)37-albumin in detecting, by dynamic contrast-enhanced magnetic resonance imaging (MRI), the effect in vivo of tamoxifen in an experimental model of breast tumor implanted in rats. MATERIALS AND METHODS: Tumors were induced by subcutaneous injection of 10 mammary adenocarcinoma cells (13762 MAT B III). Treatment with tamoxifen (or vehicle) started on day 4 after implantation. On day 10 after implantation, animals were observed by MRI using B22956/1 (or gadoteridol) and, 24 hours later, using (Gd-DTPA)37-albumin. RESULTS: Dynamic contrast-enhanced magnetic resonance imaging data showed that tamoxifen treatment decreased vascular permeability to B22956/1, whereas no difference was detectable in permeability to gadoteridol or to (Gd-DTPA)37-albumin. No effect on fractional plasma volume was detected with either of contrast agents. CONCLUSIONS: B22956/1 is superior to both small Gd chelates and macromolecular contrast agents in the assessment of the effect of tamoxifen treatment on tumor vasculature.

Effect of iomeprol on rat hippocampal slice synaptic transmission: comparison with other X-ray contrast agents.

RATIONALE AND OBJECTIVES: All contrast agents should be neurologically safe because although some are not indicated for procedures, such as myelography, just the same they may come in contact with nervous tissue during contrast-enhanced imaging. This is because even when they are intravascularly injected, the presence of undiagnosed blood-brain barrier damage may allow them to penetrate the brain barrier. In the present study, we investigated the neurologic safety of iomeprol by studying in vitro its potential effects on the central nervous system (CNS) synaptic transmission. Other widely used x-ray contrast agents were also assessed for comparative purposes. METHODS: CNS synaptic transmission was evaluated in terms of evoked field potentials recorded from the pyramidal region of rat hippocampal slices. The field potentials were evoked by electrical stimulation of the Schaffer collateral pathway. The effects of the contrast agents were evaluated in terms of number and amplitude of population spikes (PS) and as the maximal slope of the excitatory postsynaptic potentials (EPSP). The contrast agents were tested at final concentrations of 3, 10, and 30 mg(iodine)/mL in iso-osmolal condition with respect to artificial cerebrospinal fluid (CSF). RESULTS: Iomeprol, like ioversol, principally exerted a mild inhibitory effect on CNS synaptic transmission, an effect that was preceded by a weak, transient excitation. Iopentol exerted a rapid and complete inhibition of synaptic transmission without showing any excitatory effects. Iobitridol, though belonging to the nonionic monomeric class, exerted, surprisingly, an epileptogenic action at the highest concentration, whereas its inhibitory action was slow and mild. Diatrizoate, as expected, exerted an epileptogenic activity even at the lowest concentration, followed by a marked inhibitory action. Ioxaglate, as expected because it is an ionic though dimeric contrast agent, exerted an epileptogenic action at the intermediate concentration, whereas it barely demonstrated an inhibitory effect at all. All the contrast agent effects observed in the study reversed or tended to reverse during washout. CONCLUSIONS: Even taking in account the limitation because of the use of an in vitro approach and high contrast agent concentrations, we can conclude that the positive neuro-tolerability of iomeprol is further confirmed by this model as it proved to be devoid of epileptogenic activity and, among the contrast agents exhibiting inhibitory action, it was the contrast agent with the least amount of activity. In addition, contrary to that generally reported in the literature, nonionic, low osmolal contrast agents are not all identical in their neuro-tolerability when assessed in the rat hippocampal slice model.