Biomedical subjects

G N Chimon

Publications and source records attributed to G N Chimon.

4 recordsLinked to original sources

PubMed2005

Microfluidic reactor for the radiosynthesis of PET radiotracers.

Here we show the first application of a microfabricated reaction system to PET radiochemistry, we term "microfluidic PET". The short half-life of the positron emitting isotopes and the trace chemical quantities used in radiolabelling make PET radiochemistry amenable to miniaturisation. Microfluidic technologies are capable of controlling and transferring tiny quantities of liquids which allow chemical and biochemical assays to be integrated and carried out on a small scale. Such technologies provide distinct advantages over current methods of PET radiochemical synthesis. To demonstrate "proof of principle" we have investigated the radiohalogenation of small and large molecular weight molecules using the microfluidic device. These reactions involved the direct radioiodination of the apoptosis marker Annexin V using iodine-124, the indirect radioiodination of the anti-cancer drug doxorubicin from a tin-butyl precursor and the radiosynthesis of 2-[(18)F]FDG from a mannose triflate precursor and fluorine-18 and hence provide a test bed for microfluidic reactions. We demonstrate the rapid radioiodination of the protein Annexin V (40% radiochemical yield within 1 min) and the rapid radiofluorination of 2-[(18)F]FDG (60% radiochemical yield within 4s) using a polymer microreactor chip. Chromatographic analysis showed that the labelling efficiency of the unoptimised microfluidic chip is comparable to conventional PET radiolabelling reactions.

Bioreactors↗

PubMed2005

Microfluidic technology for PET radiochemistry.

This paper describes the first application of a microfabricated reaction system to positron emission tomography (PET) radiochemistry. We have applied microfluidic technology to synthesise PET radiopharmaceuticals using (18)F and (124)I as labels for fluorodeoxyglucose (FDG) and Annexin-V, respectively. These reactions involved established methods of nucleophilic substitution on a mannose triflate precursor and direct iodination of the protein using iodogen as an oxidant. This has demonstrated a proof of principle of using microfluidic technology to radiochemical reactions involving low and high molecular weight compounds. Using microfluidic reactions, [(18)F]FDG was synthesised with a 50% incorporation of the available F-18 radioactivity in a very short time of 4s. The radiolabelling efficiency of (124)I Annexin-V was 40% after 1 min reaction time. Chromatographic analysis showed that such reaction yields are comparable to conventional methods, but in a much shorter time. The yields can be further improved with more optimisation of the microfluidic device itself and its fluid mixing profiles. This demonstrates the potential for this technology to have an impact on rapid and simpler radiopharmaceutical synthesis using short and medium half-life radionuclides.

Biotechnology↗

PubMed2000

Expression of angiotensin II AT2 receptor in the acute phase of stroke in rats.

A male Wistar rat model of stroke (middle cerebral artery occlusion; MCAO) was used to study the angiotensin II (Ang II) receptor subtype 2 (AT2) gene expression by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining. After permanent occlusion of the middle cerebral artery (MCA), AT2 receptor gene expression was found to increase in the infarct cortex by 2.7-fold (1 day) and 1.7-fold (3 days), respectively. Positive AT2 immunostaining was also observed in the infarct area of the cerebral cortex. Apoptotic markers were detected in the necrotic area of the stroke cerebral cortex 1 day after MCAO. This demonstrated up-regulation of AT2 receptor may be involved in the apoptosis of tissue repair after stroke.

Acute Disease↗

PubMed1998

Ischemic tolerance and lipid peroxidation in the brain.

Using a modified method of focal ischemic preconditioning (FIP) followed by permanent middle cerebral artery occlusion (MCAO), we studied the effects of ischemic tolerance on infarct volume. The FIP was achieved by obstructing the blood flow into the MCA using miniature clamps at two points simultaneously. The first point was proximal to its origin and the second was where it intersects the middle cerebral vein. In rats subjected to three short conditioning periods (3 x 3 min with 7 min reperfusion between occlusions), there were significant reductions in the infarct volume in the cerebral cortex induced by the subsequent MCAO in FIP-treated rats compared with sham-operated controls. This rapid FIP-induced ischemic tolerance to subsequent MCAO occurred within 1 day and lasted for 5 days. Tissue lipid peroxidation in the cortex was significantly reduced for up to 2 days after FIP. In contrast, lipid peroxidation increased rapidly after MCAO. A significant reduction in this increase was observed in FIP-treated rats, suggesting a correlation with the subsequent reduction in the infarct volume.

Animals↗