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We are pleased that Dr Moshi Geso took detailed notes of our report in the March 2006 issue of the British Journal of Radiology [1]. However, his first point seems to have arisen from a misunderstanding. The report states, "The concentration of injected gold was 270 mg Au cm–3, and volume injected was 0.01 ml g–1 mouse weight" (page 249). 270 mg Au cm–3 was the gold concentration in our syringe, not the final concentration throughout the whole animal, as Dr Geso surmised ("...concentration is 270 mg Au per gram tissue"). His statement that "This means the concentration of the Au particles is around 300 times less in toxicity studies compared with imaging studies" should therefore be corrected to read, "This means the concentration of the Au particles was around 3.8 times less in the toxicity studies than in the imaging studies". The higher dose was used for imaging to clearly show the comparison with an equal amount of iodine agent, and to very clearly show the vascular retention and clearance route. We refer the reader to page 250 where we wrote, "Deliberately high amounts of gold were used to clarify printed images. CT is much more sensitive than planar imaging, and studies of high-Z agents indicate that good contrast-to-noise images can be obtained at gold concentrations of 100 µg ml–1 [14]. This level is 
100 times lower than a dose of gold nanoparticles at which we found no evidence of toxicity". At this minimal but useful concentration, the agent would be 427 times lower than the LD50 dose (e.g. in a 1.5 ml mouse blood volume, 0.1 mg ml–1 is 0.15 mg Au. For a 20 g mouse, this dose is 7.5 mg kg–1, or 427 times lower than the LD50 of 3200 mg Au kg–1). The high-contrast kidney images shown in Figure 3 were taken 1 h after intravenous injection since, at the dose used, earlier times saturated the films. Clearly a much lower dose and earlier time could have been used.
Dr Geso's suggestions that we should have plotted log concentration vs time and estimate biphasic clearance half-times thereby are well taken, as are his notices of the elevated AST (aspartate aminotransperase) and ALT (alanire aminobransferase) levels in the mouse blood 1 day after injection. However, 11 days and 28 days after injection, those elevations had subsided and no histological abnormalities of the liver were seen. Since our experiment did not explicitly control for unequal trauma to the liver from handling and restraint during intravenous injection of the individual 20 g subjects, at present we remain uncertain about the relevance of those elevations to acute pharmacological toxicity of our 1.9 nm diameter gold nanoparticles. In any case, the evidence presented suggests to us that intermediate-term toxicity is negligible or, at worst, minor.
Yours etc,
1 Nanoprobes, Inc., 95 Horse Block Road, Yaphank, NY 11980, 2 University of Connecticut Health Center, Farmington, CT 06030, USA
Received for publication August 4, 2006. Accepted for publication August 18, 2006.
References
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