Molecular Magnetic Resonance Imaging of Liver Fibrosis and Fibrogenesis Is Not Altered by Inflammation.

METHODS: Three groups of mice that develop either mild type 2 inflammation and fibrosis (wild type), severe fibrosis with exacerbated type 2 inflammation (Il10-/-Il12b-/-Il13ra2-/-), or minimal fibrosis with marked type 1 inflammation (Il4ra∂/∂) after infection with S. mansoni were imaged using both probes for determination of signal enhancement. Schistosoma mansoni-infected wild-type mice developed chronic liver fibrosis. RESULTS: The liver MR signal enhancement after either probe administration was significantly higher in S. mansoni-infected wild-type mice compared with naive animals. The S. mansoni-infected Il4ra∂/∂ mice presented with little liver signal enhancement after probe injection despite the presence of substantial inflammation. Schistosoma mansoni-infected Il10-/-Il12b-/-Il13ra2-/- mice presented with marked fibrosis, which correlated to increased signal enhancement after injection of either probe. CONCLUSIONS: Both MR probes, EP-3533 and Gd-Hyd, were specific for fibrosis in this model of chronic liver disease regardless of the presence or severity of the underlying inflammation. These results, in addition to previous findings, show the potential application of both molecular MR probes for detection and quantification of fibrosis from various etiologies.

Peroxidase Sensitive Amplifiable Probe for Molecular Magnetic Resonance Imaging of Pulmonary Inflammation.

An amplifiable magnetic resonance imaging (MRI) probe that combines the stability of the macrocyclic Gd-DOTAGA core with a peroxidase-reactive 5-hydroxytryptamide (5-HT) moiety is reported. The incubation of the complex under enzymatic oxidative conditions led to a 1.7-fold increase in r1 at 1.4 T that was attributed to an oligomerization of the probe upon oxidation. This probe, Gd-5-HT-DOTAGA, provided specific detection of lung inflammation by MRI in bleomycin-injured mice.

Evaluation of antitumor activity and cardiac toxicity of a bone-targeted ph-sensitive liposomal formulation in a bone metastasis tumor model in mice.

Chemotherapy for bone tumors is a major challenge because of the inability of therapeutics to penetrate dense bone mineral. We hypothesize that a nanostructured formulation with high affinity for bone could deliver drug to the tumor while minimizing off-target toxicity. Here, we evaluated the efficacy and toxicity of a novel bone-targeted, pH-sensitive liposomal formulation containing doxorubicin in an animal model of bone metastasis. Biodistribution studies with the liposome showed good uptake in tumor, but low accumulation of doxorubicin in the heart. Mice treated with the bone-targeted liposome formulation showed a 70% reduction in tumor volume, compared to 35% reduction for free doxorubicin at the same dose. Both cardiac toxicity and overall mortality were significantly lower for animals treated with the bone-targeted liposomes compared to free drug. Bone-targeted, pH-sensitive, doxorubicin containing liposomes represent a promising approach to selectively delivering doxorubicin to bone tumors while minimizing cardiac toxicity.

Development of imaging probes for bone cancer in animal models. A systematic review.

Bone is a dynamic tissue that is constantly remodeled throughout the lifetime to ensure the integrity of the skeleton. Primary cancer cells disseminate into circulation, often extravasating to bone, where they interact with the bone marrow to grow and proliferate, disrupting the bone homeostasis. Although primary bone tumors account for less than 0.2% of all cancers, bone is a common site for the development of metastases, as its microenvironment provides the necessary conditions for the growth and proliferation of cancer cells. Metastases to the skeletal system are observed in up to 70% of all cancer patients and the growth of disseminated tumor metastases is a major cause of mortality. As widely known, a non-invasive diagnosis of bone tumors at early stages is of great importance to provide insights that will help on the decision of therapy regimen, improving treatment outcomes. Early diagnosis of bone metastases is also an important step for establishing palliative care as they may cause serious endocrine, hematologic, neurologic and orthopedic complications as well as intolerable pain. Therefore, development of new imaging techniques, imaging moieties, and animal models to mimic these bone conditions, play an important role in improving the clinical outcome of this disease. In this review, we will briefly describe the advantages and disadvantages of the currently available imaging techniques that aim at identifying bone tumors. In addition, we will provide an update on the animal models applicable at mimicking bone tumor characteristics, as well as describe recent advances on the development of new imaging probes, in the preclinical settings including targeted nanoparticles and radiopharmaceuticals.