Determination of human absorbed dose of 201Tl(III)-DTPA-HIgG based on biodistribution data in rats

To estimate the absorbed dose in normal organs and inflammated tissue following i.v. administration of 201Tl(III)-DTPA-HIgG by using biodistribution data in inflammation-bearing rats was attempted. The percentages of injected dose per gram of each organ were calculated. The medical internal radiation dose formulation was applied to calculate the absorbed dose for various organs. The inflammated tissue to blood activity concentration ratios were about 19 and 23.3 at 24 and 28 h post-injection, respectively. A 185-MBq injection of 201Tl-DTPA-HIgG into the human body, might result in an estimated absorbed dose of 14.4 mGy for the total body and the highest absorbed dose was in the kidney with 1195 (mGy) and second to the Spleen were the liver, the lungs and the adrenals, which received 250.5 (mGy), 58.64 (mGy) and 56.44 (mGy), respectively. Biodistribution of 201Tl(III)-DTPA-HIgG demonstrated significant inflammated tissue uptake and low muscle and blood uptake, allowing for imaging of inflammated tissues. © The Author 2010. Published by Oxford University Press. All rights reserved

In vivo evaluation of riboflavin receptor targeted fluorescent USPIO in mice with prostate cancer xenografts

Riboflavin (Rf) receptors bind and translocate Rf and its phosphorylated forms (e.g. flavin mononucleotide, FMN) into cells where they mediate various cellular metabolic pathways. Previously, we showed that FMN-coated ultrasmall superparamagnetic iron oxide (FLUSPIO) nanoparticles are suitable for labeling metabolically active cancer and endothelial cells in vitro. In this study, we focused on the in vivo application of FLUSPIO using prostate cancer xenografts. Size, charge, and chemical composition of FLUSPIO were evaluated. We explored the in vitro specificity of FLUSPIO for its cellular receptors using magnetic resonance imaging (MRI) and Prussian blue staining. Competitive binding experiments were performed in vivo by injecting free FMN in excess. Bio-distribution of FLUSPIO was determined by estimating iron content in organs and tumors using a colorimetric assay. AFM analysis and zeta potential measurements revealed a particulate morphology approximately 20–40 nm in size and a negative zeta potential (–24.23 ± 0.15 mV) in water. X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry data confirmed FMN present on the USPIO nanoparticle surface. FLUSPIO uptake in prostate cancer cells and human umbilical vein endothelial cells was significantly higher than that of control USPIO, while addition of excess of free FMN reduced accumulation. Similarly, in vivo MRI and histology showed specific FLUSPIO uptake by prostate cancer cells, tumor endothelial cells, and tumor-associated macrophages. Besides prominent tumor accumulation, FLUSPIO accumulated in the liver, spleen, lung, and skin. Hence, our data strengthen our hypothesis that targeting riboflavin receptors is an efficient approach to accumulate nanomedicines in tumors opening perspectives for the development of diagnostic and therapeutic systems