MR imaging during endovascular procedures: an evaluation of the potential for catheter heating.

MRI in catheterized patients is considered unsafe due to the potential for focal heating. This concern arises from the continuous metallic braid that is incorporated into catheters to provide their desired physical properties. The potential for catheter heating during MR scanning was assessed in an in vitro model simulating a patient undergoing a neurovascular procedure in which MR scans of the brain will be performed. Heating adjacent to endovascular devices was assessed with fluoroptic temperature probes in a polyacrylamide gel. The effect of variable immersion lengths, lateral and longitudinal offsets, position along the endovascular device, physical MR system, and specific absorption rate (SAR) level were studied to determine their effect on catheter heating. A rapid temperature rise was evident next to endovascular devices during MR scanning and varied moderately with immersed length, position within the bore, measurement point on the device, and MR system used. Peak heating rates were less than 1 degree C/min with maximal SAR exposure and anatomically realistic geometries. Heating scaled linearly with SAR and SAR values below 0.2 W/kg produced negligible heating near catheters. For the evaluated application, substantial SAR restrictions, coupled with limited imaging durations, are proposed as sufficient to permit MRI without concern for thermal injury.

Anti-cancer action of 4-iodo-3-nitrobenzamide in combination with buthionine sulfoximine: inactivation of poly(ADP-ribose) polymerase and tumor glycolysis and the appearance of a poly(ADP-ribose) polymerase protease.

E-ras 20 tumorigenic malignant cells and CV-1 non-tumorigenic cells were treated with a drug combination of 4-iodo-3-nitrobenzamide (INO(2)BA) and buthionine sulfoximine (BSO). Growth inhibition of E-ras 20 cells by INO(2)BA was augmented 4-fold when cellular GSH content was diminished by BSO, but the growth rate of CV-1 cells was not affected by the drug combination. Analyses of the intracellular fate of the prodrug INO(2)BA revealed that in E-ras 20 cells about 50% of the intracellular reduced drug was covalently protein-bound, and this binding was dependent upon BSO, whereas in CV-1 cells BSO did not influence protein binding. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was identified as the protein that covalently binds the reduction product of INO(2)BA, which is 4-iodo-3-nitrosobenzamide. Since only the enzymatically reduced drug INOBA bound covalently to GAPDH, the BSO-dependent covalent protein-drug association indicated an apparent nitro-reductase activity present in E-ras 20 cells, but not in CV-1 cells, explaining the selective toxicity. Covalent binding of INOBA to GAPDH inactivated this enzyme in vitro; INO(2)BA+BSO also inactivated cellular glycolysis in E-ras 20 cells because it provided the precursor to the inhibitory species: INOBA. Another event that occurred in INO(2)BA+BSO-treated E-ras 20 cells was the progressive appearance of a poly(ADP-ribose) polymerase protease. This enzyme was partially purified and characterized by the polypeptide degradation product generated from PARP I, which exhibited a 50kDa mass. This pattern of proteolysis of PARP I is consistent with a drug-induced necrotic cell killing pathway.