Development of Microfluidic Plasma Counting System for Small Animal Molecular Imaging Using PET --- Measurement of Small Radioactivity Concentration

[Introduction] The system for uL-ordered blood sampling and plasma radioactiveconcentration measurement, Microfluidic Mouse Plasma Counting System (uFmPC, patent pending), isdeveloping. uFmPC should measure very small radioactivity concentration, from several to hundreds Bq/uL.This study aimed to investigate the accuracy on such small radioactivity concentration. [Method] In uFmPC,blood was sampled using microfluidic technique, and it was stocked in channels on a plastic disc (CD-Well).The blood was then separated by rotating the disc. Because the channels had exact cross-sectional area of0.067 mm2, the volumes of blood and separated plasma could be derived by measurement of the lengthusing a flatbed scanner. The amount of radioactivity was acquired by a storage phosphor screen. In theexperiments, one and three uL of FDG solutions containing the radioactivity ranging from 4 to 128 Bq/uLwere introduced in the channels. The radioactivity was measured using Imaging Plate (IP) and BAS-5000(Fujifilm Corp., Japan) with 120-minute exposure. CD-Well was also scanned by GT-X970 scanner (SeikoEPSON, Japan) in 2400 dpi in order to measure the volume of solution. The activity concentration of givenFDG was compared with a photo-stimulated luminescence value (PSL) derived from uFmPC. [Results andDiscussion] Measured images were shown in Fig. 1: a scanned image (A) and an image from IP (B). Theposition of introduced FDG was detected as shown in (C) with black thick curves, and it was applied to theIP image to read out an amount of radioactivity. (D) was a superimposed image. From 120-minute exposure,the PSL was correlated with the given concentration well (y = 1.8x + 4.4 for 1 uL case and y = 2.1x + 6.6 for3 uL case. r2=1.00 for both cases). We can conclude that the concept of uFmPC had potential to measuresmall radioactivity concentration.2009 World Molecular Imaging Congres

Development of Microfluidic Plasma Counting System for Small Animal Molecular Imaging Using PET - Principle Validation for Blood Transportation System

2009 World Molecular Imaging Congres

Novel system using microliter order sample volume for measuring arterial radioactivity concentrations in whole blood and plasma for mouse PET dynamic study

This study aimed to develop a new system, named CD-Well, for mouse PET dynamic study. CD-Well allows the determination of time-activity curves(TACs) for arterial whole blood and plasma using 2-3 muL of blood per sample;the minute sample size is ideal for studies in small animals. The system has the following merits: (1)measures volume and radioactivity of whole blood and plasma separately; (2) allows measurements at 10 s intervals to capture initial rapid changes in the TAC; and (3) is compact and easy to handle, minimizes blood loss from sampling, and delay and dispersion of the TAC. CD-Well has 36 U-shaped channels. A drop of blood is sampled into the opening of the channel and stored there. After serial sampling is completed, CD-Well is centrifuged and scanned using a flatbed scanner to define the regions of plasma and blood cells. The length measured is converted to volume because the channels have a precise and uniform cross section. Then, CD-Well is exposed to an imaging plate to measure radioactivity. Finally, radioactivityconcentrations are computed. We evaluated the performance of CD-Well in in vitro measurement and in vivo 18F-fluorodeoxyglucose and [11C]2-carbomethoxy-3beta-(4-fluorophenyl) tropane studies. In in vitro evaluation, per cent differences (mean+-SE) from manual measurement were 4.4+-3.6% for whole blood and 4.0+-3.5% for plasma across the typical range of radioactivity measured in mouse dynamic study. In in vivo studies, reasonable TACs were obtained. The peaks were captured well, and the time courses coincided well with the TAC derived from PET imaging of the heart chamber. The total blood loss was less than 200 muL, which had no physiological effect on the mice. CD-Well demonstrates satisfactory performance, and is useful for mouse PETdynamic study

Categorization of nano-structured titanium dioxide according to physicochemical characteristics and pulmonary toxicity

A potentially useful means of predicting the pulmonary risk posed by new forms of nano-structured titanium dioxide (nano-TiO2) is to use the associations between the physicochemical properties and pulmonary toxicity of characterized forms of TiO2. In the present study, we conducted intratracheal administration studies in rats to clarify the associations between the physicochemical characteristics of seven characterized forms of TiO2 and their acute or subacute pulmonary inflammatory toxicity. Examination of the associations between the physicochemical characteristics of the TiO2 and the pulmonary inflammatory responses they induced revealed (1) that differences in the crystallinity or shape of the TiO2 particles were not associated with the acute pulmonary inflammatory response; (2) that particle size was associated with the acute pulmonary inflammatory response; and (3) that TiO2 particles coated with Al(OH)3 induced a greater pulmonary inflammatory response than did non-coated particles. We separated the seven TiO2 into two groups: a group containing the six TiO2 with no surface coating and a group containing the one TiO2 with a surface coating. Intratracheal administration to rats of TiO2 from the first group (i.e., non-coated TiO2) induced only acute pulmonary inflammatory responses, and within this group, the acute pulmonary inflammatory response was equivalent when the particle size was the same, regardless of crystallinity or shape. In contrast, intratracheal administration to rats of the TiO2 from the second group (i.e., the coated TiO2) induced a more severe, subacute pulmonary inflammatory response compared with that produced by the non-coated TiO2. Since alteration of the pulmonary inflammatory response by surface treatment may depend on the coating material used, the pulmonary toxicities of coated TiO2 need to be further evaluated. Overall, the present results demonstrate that physicochemical properties may be useful for predicting the pulmonary risk posed by new nano-TiO2 materials. Keywords: Nano materials, Titanium dioxide, Intratracheal administration, Pulmonary toxicity, Risk assessmen