Fred W. Teare

Electrochemical monofluorination of pyridine: synthesis of 2-fluoropyridine at a platinum anode☆

2-Fluoropyridine has been synthesized in 22% yield by electrochemical fluorination of pyridine at a platinum anode at 2.5 V vs Ag/Ag+ (0.1 M) and with 0.5 M tetramethylammonium dihydrogen trifluoride (Me4NF·2HF) in dry acetonitrile as supporting electrolyte and fluoride source. At lower ME4NF·2HF concentrations and at lower applied potentials both yield and reaction rate are decreased whereas at higher potentials the supporting electrolyte/solvent system decomposes. The choice and purity of supporting electrolyte is an important factor in determining the product distribution and yield. The relatively low fluoride concentration allows use of a glass cell.

Radiofluorination with reactor-produced Cesium [18F]fluoride: No-carrier-added [18F]2-fluoronicotine and [18F]6-fluoronicotine

Abstract We have synthesised no-carrier-added [18F]2-fluoronicotine by the halogen-exchange reaction of reactor-produced Cs18F upon 2-bromonicotine in refluxing DMSO. No special drying of the Cs18F was required. [18F]2-Fluoronicotine was isolated by reversed-phase HPLC and production of 220 MBq (6 mCi) ready for injection represented a decay-corrected radiochemical yield of 23% and required 3.5 h from end-of-bombardment. Similarly, [18F]6-fluoronicotine was prepared from 6-bromonicotine in amounts of 80 MBq (2.2 mCi) or 8% yield. These quantities are sufficient for studies in humans.

Acute effect of cadmium on hepatic drug-metabolizing enzymes in the rat☆

Abstract Single ip injections of cadmium chloride at doses of 2.5 or 3.75 mg/kg (equivalent to 1.5 or 2.3 mg of Cd, respectively) into male Wistar rats of mean body weight of 226 ± 17 g produced significant inhibition (25–60%) of aniline hydroxylase and nitroreductase activity and also lowered the microsomal cytochrome P-450 content to 50% of the control value. These effects are in contrasto those on O-demethylase activity, which was not inhibited by either dose of cadmium chloride when enzyme activities were subsequently measured in a 0.05 m phosphate-buffered incubation system. However, the opposite conclusion was reached for the effect of these same doses of cadmium chloride when O-demethylase activity was assessed in comparable Tris-buffered systems. There appears to be a definite “buffer effect” in operation here. While the higher dose of this toxic metal salt significantly reduced the activities of the phenobarbital-induced hepatic microsomal drug-metabolizing enzymes and of cytochrome P-450, the lower dose was without significant effect on this induction, with the one exception of aniline hydroxylase when assessed in a Tris-buffer system.

A novel rapid thin-layer chromatographic monitoring system for the radioiodination of protein and polypeptides

Abstract A modified instant thin-layer chromatographic system is described which enables the degree of iodination to be determined during a radioiodination procedure that normally extends over a period greater than 5 min. The technique is ideally suited to radioiodinations employing a “dilute” chloramine-T method (1) or a lactoperoxidase method (2) or employing electrochemical (3) means. The equipment is extremely simple and readily available. The complete assay may be performed in a period of 3 min. the results agree extremely well with those obtained by gel exclusion chromatography. The method is precise and inexpensive.

Short- and long-term cadmium distribution in rat livers after different routes of administration

Intracellular hepatic distribution of cadmium in male Wistar rats were determined after various time intervals up to 6 months following a single intraperitoneal injection of cadmium chloride (3.75 mg/kg). After an initial liver accumulation period of approximately 2 weeks, cadmium was slowly eliminated. This decrease occurred primarily in the soluble fraction, but also to a lesser extent in the nuclear and mitochondrial fractions. No detectable decrease of cadmium was observed in the microsomal fraction. There was no apparent redistribution of cadmium within these hepatic fractions during the 6-month period of study. A comparison of the intracellular cadmium distribution following administration by intraperitoneal, oral, and pulmonary routes revealed that in each instance the soluble fraction contained the greatest amount of this element by far with decreasing amounts in the microsomes, mitochondria, and nuclei in that order.

Micro-electrolytic radioiodination of polypeptide hormones to high specific activity

Abstract Electrolytic radioiodination employs a d.c. constant current or constant voltage source to generate an active radioiodine species, at a large surfaced platinum anode, to label tyrosine and histidine-containing compounds. This simple micro-electrolytic method, under carefully controlled conditions of pH, temperature, reaction time, current and anode potential has been shown to be reproducible and to yield labelled hormone preparations of high specific activity, which retain biological as well as immunological activity. A new platinum microcell was designed for this purpose. ‡

[125I]7-iodo-6-demethyl-6-deoxytetracycline HCL: Its use in the study of bone mineralization

Abstract [ 125 I]7-iodo-6-demethyl-6-deoxytetracycline can be used in a non-invasive method to indicate sites of active bone mineralization. Sequential doses of this agent have been used to follow bone repair in a fractured femur of a dog without resorting to bone biopsy. Metabolic problems that involve bone may also be studied with this potentially useful radiopharmaceutical.