Tumor specific MRI contrast agents are in development to provide better delineation and progression information for various tumors. Clinical oncology has a need for contrast agents that can identify tumors and metastases at a size of 100,000 cells rather than 1,000,000,000 cells. This level of sensitivity requires excellent tumor targeting of imaging agents and a high MRI signal.
Tumor specific agents accumulate at pathological tissues by passive or active targeting mechanisms. Passive targeting agents use e.g., the natural defense mechanisms in which phagocytic cells remove foreign particles from the body. Active targeting is based on a ligand-directed, site-specific accumulation of contrast agents. The availability of macromolecular contrast agents such as feruglose and ultrasmall superparamagnetic iron oxide (USPIO), which permit the assessment of tissue permeability, may also improve the detection of tumor grade, tumor type, and response to drugs that target angiogenesis.

See also Monoclonal Antibodies, Metalloporphyrins, Nitroxides and Ferrioxamine.

Blood pool agents (intravascular contrast agents) remain in the blood for a prolonged time compared with conventional contrast agents, which diffuse quickly into the interstitial space. Magnetic resonance angiography (MRA), cardiovascular imaging, or contrast enhanced MRIs are possible over an hour or more. This advantage over conventional MRI contrast media allows also higher resolution MRA of several territories using respiratory or cardiac gating techniques with a single contrast bolus.
Different types of blood pool contrast agents:
Blood pool MRI contrast agents with their longer intravascular circulation can be designed to be targeted to necrotic myocardium, to assess myocardial viability, or tumor directed to provide better diagnostic information for various tumors. A disadvantage of the use of blood pool agents for MRA is that the separation of arteries and veins is more difficult because they are present in both and the overlapping of those vessels is disturbing. This can be solved by e.g. different MIP segmentation algorithms.

See also Necrosis Avid Contrast Agent, Tumor Specific Agents, Feruglose, Gadofosveset Trisodium (Vasovist), Ultrasmall Superparamagnetic Iron Oxide and Contrast Medium.

Eovist® (other brand name Primovist™) is a organ specific MRI contrast agent for the imaging, detection and characterization of liver conditions, including liver tumors, cysts, as well as other malignant and benign lesions. It is a water-soluble ethoxybenzyl derivative of Gd-DTPA. This compound is taken up by the hepatocytes (approximately 30% of the dose goes to the hepatocytes) and is equally excreted renal and biliary in humans. Excretion of Gd-EOB-DTPA in the bile may also permit visualization of both the gall bladder and the bile ducts.
Eovist® brightens the signal of T1 weighted MR images immediately after contrast administration. Dynamic and accumulation phase imaging can also be performed after bolus injection of Eovist®. The hepatocytes uptake will increase the signal intensity of normal liver parenchyma at 10 to 20 minutes after injection. This results in improved lesion-to-liver contrast because malignant tumors (metastases, the majority of hepatocellular carcinomas) do not contain either hepatocytes or their functioning is hampered.

WARNING: Gadolinium-based contrast agents increase the risk for nephrogenic systemic fibrosis (NSF) in patients with acute or chronic severe renal insufficiency (glomerular filtration rate less than 30 mL/min/1.73m²), or acute renal insufficiency of any severity due to the hepato-renal syndrome or in the perioperative liver transplantation period.

See also Drug Development and Approval Process USA, Contrast Medium, Hepatobiliary Contrast Agents, Tumor Specific Agents and Molecular Imaging.

Short name: (Gd-DTPA)-17, 24 cascade polymer, generic name: Gadomer-17, 24, central moiety: Gd2+, relaxivity: r1=11.9, B0=1.0 T, r2=16.5, Dose: 0.05 mmol/kg
An intravascular macromolecular MRI contrast agent with positive enhancement under development (Bayer Schering Pharma AG) for MR angiography and tumor differentiation. The synthetic dendrimer with large molecular weight (17kD - limits agent to vascular space) is linked to Gadolinium. The renal excretion is slowed to intermediate molecular size. In MRA a longer lasting venous and arterial enhancement was seen with Gadomer-17 due to the particular pharmacokinetics of this agent.

See also Tumor Specific Agents, and Intravascular Contrast Agents.

Porphyrins occur naturally in plants and animals. All porphyrin molecules feature an aromatic macrocycle ring with a central binding site. This site accommodates transition metals, which are held in place by inward-facing nitrogen atoms. Metalloporphyrins have usually a low toxicity and a potential of a selective uptake in tumors or necrosis. These properties are advantageous for a use as MRI tumor specific agents with positive enhancement. These contrast agents enhance tumors on T1 weighted sequences, which are isointense to surrounding tissues. Porphyrin-based compounds have also necrosis avid properties; they can depict the extent of myocardial infarction as defined by histopathology.
Metalloporphyrins are also used in photodynamic therapy of tumors. The compounds contain a 'lone star' metal atom at the center of the ring and are 'bigger than the average porphyrin'. They contain five N atoms in the central chelating core and this allows them to form complexes with large trivalent lanthanide metals, which have useful cancer therapy properties.

See also Classifications, Characteristics, etc., Gadophrin, MnIIITPPS4, Necrosis Avid Contrast Agent.