The Non-Anhydrous, Minimally Basic Synthesis of the Dopamine D Agonist [18F]MCL-524.

The dopamine D agonist MCL-524 is selective for the D receptor in the high-affinity state (D), and, therefore, the PET analogue, [F]MCL-524, may facilitate the elucidation of the role of D in disorders such as schizophrenia. However, the previously reported synthesis of [F]MCL-524 proved difficult to replicate and was lacking experimental details. We therefore developed a new synthesis of [F]MCL-524 using a "non-anhydrous, minimally basic" (NAMB) approach.

Mitochondrial transplantation by intra-arterial injection for acute kidney injury.

Acute kidney injury is a common clinical disorder and one of the major causes of morbidity and mortality in the postoperative period. In this study, the safety and efficacy of autologous mitochondrial transplantation by intra-arterial injection for renal protection in a swine model of bilateral renal ischemia-reperfusion injury were investigated. Female Yorkshire pigs underwent percutaneous bilateral temporary occlusion of the renal arteries with balloon catheters.

A non-anhydrous, minimally basic protocol for the simplification of nucleophilic F-fluorination chemistry.

Fluorine-18 radiolabeling typically includes several conserved steps including elution of the [F]fluoride from an anion exchange cartridge with a basic solution of KCO or KHCO and Kryptofix 2.2.2.

A Novel Biological Strategy for Myocardial Protection by Intracoronary Delivery of Mitochondria: Safety and Efficacy.

Mitochondrial dysfunction is the determinant insult of ischemia-reperfusion injury. Autologous mitochondrial transplantation involves supplying one's healthy mitochondria to the ischemic region harboring damaged mitochondria. The authors used in vivo swine to show that mitochondrial transplantation in the heart by intracoronary delivery is safe, with specific distribution to the heart, and results in significant increase in coronary blood flow, which requires intact mitochondrial viability, adenosine triphosphate production, and, in part, the activation of vascular K channels.

Mitochondrial transplantation enhances murine lung viability and recovery after ischemia-reperfusion injury.

The most common cause of acute lung injury is ischemia-reperfusion injury (IRI), during which mitochondrial damage occurs. We have previously demonstrated that mitochondrial transplantation is an efficacious therapy to replace or augment mitochondria damaged by IRI, allowing for enhanced muscle viability and function in cardiac tissue. Here, we investigate the efficacy of mitochondrial transplantation in a murine lung IRI model using male C57BL/6J mice.

Mitochondrial transplantation prolongs cold ischemia time in murine heart transplantation.

Background: Cold ischemia time (CIT) causes ischemia‒reperfusion injury to the mitochondria and detrimentally effects myocardial function and tissue viability. Mitochondrial transplantation replaces damaged mitochondria and enhances myocardial function and tissue viability. Herein we investigated the efficacy of mitochondrial transplantation in enhancing graft function and viability after prolonged CIT.

New chemical and radiochemical routes to [F]Rho6G-DEG-F, a delocalized lipophilic cation for myocardial perfusion imaging with PET.

New chemical and radiochemical syntheses are described for the preparation of [F]Rho6G-DEG-F, an F-labeled analogue of the fluoresecent dye rhodamine 6G, which has shown promise as myocardidal perfusion imaging agent. Tosylated precursors of [F]Rho6G-DEG-F amenable to F-labeling were obtained either through a two-step synthesis from rhodamine 6G lactone (33% yield), or in one step from rhodamine 575 (64% yield), then purified by preparative C chromatography. Manual synthesis of [F]Rho6G-DEG-F was achieved in a single radiochemical step from either the tosylate salt or the tosylate/formate double salt in DMSO under standard nucleophillic aliphatic F-fluorination conditions (K[F]F/KCO/Kryptofix 2.

Preclinical validations of [F]FPyPEGCBT-(RGDfK): a F-labelled RGD peptide prepared by ligation of 2-cyanobenzothiazole and 1,2-aminothiol to image angiogenesis.

Background: αβ, αβ and αβ integrins are known to be involved in carcinogenesis and are overexpressed in many types of tumours compared to healthy tissues; thereby they have been selected as promising therapeutic targets. Positron emission tomography (PET) is providing a unique non-invasive screening assay to discriminate which patient is more prone to benefit from antiangiogenic therapies, and extensive research has been carried out to develop a clinical radiopharmaceutical that binds specifically to integrin receptors. We recently reported the synthesis of a new F-labelled RGD peptide prepared by 2-cyanobenzothiazole (CBT)/1,2-aminothiol conjugation.

Magnetic Droplet Microfluidics as a Platform for the Concentration of [18F]Fluoride and Radiosynthesis of Sulfonyl [18F]Fluoride.

The radioisotope 18F is often considered the best choice for positron emission tomography (PET) owing to its desirable chemical and radiochemical properties. However, nucleophilic 18F-fluorination of large, water-soluble biomolecules, based on C-F bond formation, has traditionally been difficult. Thus, several aqueous fluorination approaches that offer significant versatility in radiopharmaceutical synthesis with sensitive targeting vectors have been developed.

A novel 2-cyanobenzothiazole-based (18)F prosthetic group for conjugation to 1,2-aminothiol-bearing targeting vectors.

In a bid to find an efficient means to radiolabel biomolecules under mild conditions for PET imaging, a bifunctional (18)F prosthetic molecule has been developed. The compound, dubbed [(18)F]FPyPEGCBT, consists of a 2-substituted pyridine moiety for [(18)F]F(-) incorporation and a 2-cyanobenzothiazole moiety for coupling to terminal cysteine residues. The two functionalities are separated by a mini-PEG chain.

2-Fluoropyridine prosthetic compounds for the 18F labeling of bombesin analogues.

Acetylene-bearing 2-[(18)F]fluoropyridines [(18)F]FPy5yne and PEG-[(18)F]FPyKYNE were prepared via efficient nucleophilic heteroaromatic [(18)F]fluorination of their corresponding 2-trimethylammoniumpyrdinyl precursors. The prosthetic groups were conjugated to azide- and PEG3-modified bombesin(6-14) analogues via copper-catalyzed azide-alkyne cycloaddition couplings to yield mono- and di-mini-PEGylated ligands for PET imaging of the gastrin- releasing peptide receptor. The PEG3- and PEG2/PEG3-bearing (18)F peptides showed decreased lipophilicity relative to an analogous non-mini-PEGylated (18)F peptide.

Sulfonyl fluoride-based prosthetic compounds as potential 18F labelling agents.

Nucleophilic incorporation of [(18)F]F(-) under aqueous conditions holds several advantages in radiopharmaceutical development, especially with the advent of complex biological pharmacophores. Sulfonyl fluorides can be prepared in water at room temperature, yet they have not been assayed as a potential means to (18)F-labelled biomarkers for PET chemistry. We developed a general route to prepare bifunctional 4-formyl-, 3-formyl-, 4-maleimido- and 4-oxylalkynl-arylsulfonyl [(18)F]fluorides from their sulfonyl chloride analogues in 1:1 mixtures of acetonitrile, THF, or tBuOH and Cs[(18)F]F/Cs(2)CO(3(aq.

Labeling of an antisense oligonucleotide with [(18)F]FPy5yne.

Functional imaging of gene expression in vivo with short-lived positron emitter (18)F remains an unrealized goal, in part because the long reaction times and challenging protocols typically required to label nucleic acid-based molecular probes with this radionuclide (t(1/2) = 109.8 minutes). To this end, we synthesized prosthetic group 2-[(18)F]fluoro-3-(hex-5-ynyloxy)pyridine ([(18)F]FPy5yne), used previously to label peptides, and coupled it to an oligodeoxyribonucleotide with (18)F by way of a Cu(I)-mediated azide/alkyne cycloaddition reaction.

Long-term survival of arteriovenous fistulas in home hemodialysis patients.

Background: We report the outcome of arteriovenous (AV) fistulas created and managed by a multidisciplinary team in patients on hemodialysis (HD) over 20 years.

Methods: We analyzed 432 AV fistulas in 301 home HD patients (12% diabetic; median age 47 years) followed for up to 161 months. Observed end points were spontaneous or surgical AV fistula closure, or construction of a new vascular anastomosis.

Audit of the outcome of patients with renal failure presenting to a regional nephrology service.

Aim: To assess the outcome of patients with renal failure presenting to a regional nephrology unit.

Methods: The records of patients with plasma creatinine concentration > or = 0.30 mmol/L who presented between 1 January 1988 and 31 December 1993, or were already under follow up, were studied.

Hemorheology and fistula function in home hemodialysis patients following erythropoietin treatment: a prospective placebo-controlled study.

The beneficial effect of correcting anemia in end stage renal failure using recombinant human erythropoietin (rHuEPO) is sometimes complicated by thrombosis of the arteriovenous fistula. This placebo-controlled study investigated the relationship between hemorheological changes caused by rHuEPO and alterations in fistula function and heparin requirements in home hemodialysis patients. Erythropoietin induced a rise in high shear rate blood viscosity, a determinant of blood flow in large vessels.

Influence of protein nutrition on the response of growing lambs to exogenous bovine growth hormone.

Interactions between protein supply and the anabolic response to exogenous bovine (b) GH have been examined in two experiments using 28-35 kg lambs sustained entirely by intragastric infusion of volatile fatty acids (700 kJ/kg W 0.75 per day) into the rumen and the casein (600 mg (low protein; LP) or 1200 mg (high protein; HP)/kg W 0.75 per day) into the abomasum.

The effect of clenbuterol on basal protein turnover and endogenous nitrogen loss of sheep.

Seven measurements of the effect of clenbuterol on basal nitrogen excretion (UNE), and protein turnover were made in six female sheep. The sheep were sustained by the intraruminal infusion of energy as volatile fatty acids to provide maintenance, but given no protein (N-free) for 12 d (6 d control, 6 d clenbuterol). Clenbuterol reduced UNE by 20%, but only on day 2 of the 6 d subperiod.

Anaesthesia in babies with congenital dystrophia myotonica.

The anaesthetic procedures used in two babies with congenital dystrophia myotonica are described, and the problems of providing anaesthesia in patients with the adult and congenital forms of the condition discussed.

Tracheostomy tube connections for infant patients.

Attachments to tracheostomy tubes for infant patients are described. These ensure that secure fixation in the optimal position is attained and, in the semi-permanent tracheostomy, prevent accidental occlusion of the tracheostome.