Combidex® is the brand name (same as Sinerem®) for an ultrasmall superparamagnetic iron oxide (USPIO) in the development pipeline to detect metastatic disease in lymph nodes. Metastatic lymph nodes show less uptake of this MRI contrast agent, which results in less signal decrease and allows the differentiation of normal lymph nodes from normal-sized, metastatic nodes. Combidex® has also potential to be used as a functional molecular imaging agent.
In March 2005, AMAG Pharmaceuticals Inc received an approvable letter from the U.S. Food and Drug Administration with respect to Combidex subject to certain conditions.
See also Ferumoxtran, Drug Development and Approval Process USA, Molecular Imaging and Classifications, Characteristics, etc.

Contrast agents are chemical substances introduced to the anatomical or functional region being imaged, to increase the differences between different tissues or between normal and abnormal tissue, by altering the relaxation times. MRI contrast agents are classified by the different changes in relaxation times after their injection.
The design objectives for the next generation of MR contrast agents will likely focus on prolonging intravascular retention, improving tissue targeting, and accessing new contrast mechanisms. Macromolecular paramagnetic contrast agents are being tested worldwide. Preclinical data shows that these agents demonstrate great promise for improving the quality of MR angiography, and in quantificating capillary permeability and myocardial perfusion.
Ultrasmall superparamagnetic iron oxide (USPIO) particles have been evaluated in multicenter clinical trials for lymph node MR imaging and MR angiography, with the clinical impact under discussion. In addition, a wide variety of vector and carrier molecules, including antibodies, peptides, proteins, polysaccharides, liposomes, and cells have been developed to deliver magnetic labels to specific sites. Technical advances in MR imaging will further increase the efficacy and necessity of tissue-specific MRI contrast agents.

See also Adverse Reaction and Nephrogenic Systemic Fibrosis.

See also the related poll result: 'The development of contrast agents in MRI is'

DAB-Am64-(1B4M-Gd)64 is a new macromolecular MRI contrast agent for the diagnosis of liver micro-metastasis, consisting of a polypropylenimine diaminobutane (DAB) dendrimer conjugated with a bifunctional DTPA derivative complexing Gd(III).

Knee and shoulder MRI exams are the most commonly requested musculoskeletal MRI scans. Other MR imaging of the extremities includes hips, ankles, elbows, and wrists. Orthopedic imaging requires very high spatial resolution for reliable small structure definition and therefore places extremely high demands on SNR.
Exact presentation of joint pathology expects robust and reliable fat suppression, often under difficult conditions like off-center FOV, imaging at the edge of the field homogeneity or in regions with complex magnetic susceptibility.
MR examinations can evaluate meniscal dislocations, muscle fiber tears, tendon disruptions, tendinitis, and diagnose bone tumors and soft tissue masses. MR can also demonstrate acute fractures that are radiographically impossible to see. Evaluation of articular cartilage for traumatic injury or assessment of degenerative disease represents an imaging challenge, which can be overcome by high field MRI applications. Currently, fat-suppressed 3D spoiled gradient echo sequences and density weighted fast spin echo sequences are the gold-standard techniques used to assess articular cartilage.
Open MRI procedures allow the kinematic imaging of joints, which provides added value to any musculoskeletal MRI practice. This technique demonstrates the actual functional impingements or positional subluxations of joints. In knee MRI examinations, the kinematical patellar study can show patellofemoral joint abnormalities.

See also Open MRI, Knee MRI, Low Field MRI.

Liver imaging with gadolinium contrast enhanced MRI is sometimes not sufficient for a reliable diagnosis of liver lesions. For this reasons, special liver Contrast agents that are targeted to the reticuloendothelial system (RES), have been developed to improve both detection and characterization of liver and spleen lesions. Reticuloendothelial Contrast Agents, as e.g. superparamagnetic iron oxides (SPIO), are taken up by healthy liver tissue but not tumors.
These RES targeted contrast agents provide a prolonged imaging window and enough time for high spatial resolution or multiple breath hold images. Reticuloendothelial contrast agents have an increased sensitivity for the detection of small liver lesions (e.g., metastases), compared with gadolinium enhanced MRI and spiral CT. At higher field strengths with an increased signal to noise ratio the susceptibility effect with iron oxide particles may be enhanced.
Other new agents (Gadobenate Dimeglumine, Gadoxetic Acid) have both an initial extracellular circulation and a delayed liver-specific uptake. Since a considerable part of these contrast agents is excreted in the bile, functional biliary imaging can diagnose biliary anomalies, postoperative bile leaks, and anastomotic strictures. Other agents, such as liposomes (with encapsulated Gd-DTPA) or DOTA complexes are in different development stages.

See also Hepatobiliary Contrast Agents, Gadolinium Oxide, Superparamagnetic Iron Oxide and Liposomes.