![]() Nitroxides are chemically stable and show limited in vivo metabolism. Their ease of conjugation to various biomolecules makes them attractive for targeting to various organ systems. They do not cross an intact blood brain barrier and undergo glomerular filtration as a dominant route of elimination. The pharmacokinetics of nitroxides are similar to iodinated contrast agents and Gd- DTPA. They generally consist of a six- member ring piperidine derivative or a five-member ring pyrroxamide derivative. Nitroxide stable free radicals or nitroxyl spin labels as they may be called, are chemically stable organic compounds that have an unpaired electron that results in paramagnetic properties. Incidentally, the fluorescent and tumor localizing characteristics of porphyrin derivatives have been exploited in phototherapy of tumors. This material appears to work best with tumors that are isointense to surrounding structures on T1-weighted sequences. A safety ratio of about 6:1 is estimated in mice. ![]() The metalloporphyrin most commonly used as a MRI contrast agent is Mn(III)TPPS4 (manganese(III) tetra- porphyrin) because of its low toxicity (compared to Fe(III)TPPS4 for example). ![]() Mixed success has been obtained in rodents with implanted neuroblastoma and human colon carcinoma. This allows the use of 1-10 nmol concentrations of the McAb coated magnetite particles. The magnetic moment of these superparamagnetic particles is about 1000 times that of comparable paramagnetic particles. The magnetite cores are 10-20 nm in diameter with a total particle diameter of 20-32 nm. Implanted human colon carcinoma tumors in mice have been successfully imaged by using monoclonal antibodies with a large number of Gd-DTPA molecules attached.Īdditional studies report the use of very small magnetite particles coated with McAb. This problem can be addressed in several ways: 1) increasing the number of paramagnetic ions attached to the McAb 2) attaching several paramagnetic ions to a macromolecule that in turn is attached to a McAb 3) using more antibodies or those with an affinity to many antigenic sites per cell or both and 4) using a superparamagnetic particle attached to the McAb. Monoclonal antibodies (McAb) are used successfully in nuclear medicine for localization of tumors but an initial attempt at extending this use to MRI with paramagnetic (Gd3+) labeled antibodies was unsuccessful because of the estimated 800-fold lesser sensitivity of MRI. ![]()
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