A controlled study involving human subjects, designed to evaluate prospectively the safety and effectiveness of new drugs or devices or of behavioral interventions.

An agent currently in Phase III clinical trials that selectively targets diseased cells because they have increased rates of metabolism. Once inside the diseased cell, motexafin gadolinium may work to disrupt its energy production and the ability to repair itself. This biolocalization can be confirmed because the compound can be seen via MRI. Motexafin gadolinium accumulates in diseased cells with repeat doses and remains in the cells for days.
Motexafin gadolinium is being investigated in clinical trials, in combination chemotherapy and with radiation therapy for the treatment of several types of cancer.

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'

Different stages of the drug development and approval process in the USA, lead from preclinical trials (testing in animals), first application in humans through limited and broad clinical tests, to postmarketing studies.

By Dale E. Wierenga, Ph.D. and C. Robert Eaton
Office of Research and Development
Pharmaceutical Manufacturers Association

'In reviewing this report, it is important to keep in mind the realities of the drug discovery and development process. The U.S. system of new drug approvals is perhaps the most rigorous in the world. On average, it costs a company $359 million to get one new medicine from the laboratory to the pharmacist's shelf, according to a February 1993 report by the Congressional Office of Technology Assessment.'

See also Phase 1 2 3 4 Drug Trials, Food and Drug Administration, and European Medicines Agency.

Ferrioxamines are potential iron oxide-based intravascular contrast agents. Ferrioxamine methanesulfonate, ferrioxamine-B, and hydroxyethyl-starch-ferrioxamine have been tested as MRI contrast agents, partly in clinical trials.
Ferrioxamine methanesulfonate was tested as a paramagnetic agent for the imaging of the kidney and the urogenital system. Hydroxyethyl-starch-ferrioxamine has the potential to provide information regarding myocardial vascular flow and ferrioxamine-B derivatives may be used as hepatobiliary contrast agents.

See also Superparamagnetic Iron Oxide, Hepatobiliary Contrast Agents.