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In order to study “in vivo” opiate receptors, a method for11C labelling of etorphine is described. 80 mCi (max. 120 mCi) of injectable labelled product radiochemically and chemically pure, are obtained in 25 minutes with a specific activity of 800 mCi/μmol.

The feasibility of studying myocardium muscarinic receptors, non invasively, in a “live” being can be demonstrated using positron emission tomography (PET) and a ligand labelled by carbon 11, an externally detectable short lived radionuclide. Criteria necessary for in vitro characterization of muscarinic receptors by a specific ligand were verified in vivo by this method. This demonstration was carried out after injecting in a baboon, high specific activity 11 C-MQNB (the methiodide salt of quinuclidinyl benzylate) a muscarinic antagonist drug, and displacing the radioactive ligand by increasing amounts of atropine. Displacement was proportionnal to the dose of atropine and a correlation was observed between displacement and pharmacological activity (increase of heart rate). Stereospecificity of the binding was also demonstrated by using two stereoisomers of benzetimide : dexetimide and levetimide.

It is often necessary to obtain certain 11C radiopharmaceuticals with a high specific activity (> 1000 Ci/mmole), especially when these are intended for medical purposes and are either toxic or used for “in vivo” specific receptor binding studies. The amounts of labelling agent must be very small (concentrations often below to 10−3 M) and some synthesis are difficult or impossible under these conditions. —This article shows how the specific activitry of the labelling agent A affects the synthesis yield of the radiopharmaceutical A′ in the reaction: —A specific activity increase can improve, reduce or have no effect on the yield according to the respective valuse of V1, V2, V′1, V′2. —Different ways to shift an epuilibrium unfavourabel to labelling are also given : reaction temperature, concentrations, addition of starting products, removal of final products. —The reaction kinetics are important since the half-life of carbon 11 is 20 mn, but this parameter is a complex function of concentrations which can only be detemined by experiment. It seems however that in special cases the percentage of radioactivity incorporated in a given times is imdependent of specific activity. —The effect of impurities, which can be present in concentration of the same order of magnitude as those of the labelling agent is also discussed. —Each thereticl development is illustrated by concrete examples studied in the laboratory. —The conclusion is that theoretically it should not be impossible to synthesize strictly carrier-free 11C radiopharmaceuticals in certain favourable cases (if it were known how to prepare such carrier-free labelling agents).

The distribution and kinetics of [11C]flunitrazepam in the brain were studied by positron emission tomography in the living baboon. Flunitrazepam was labelled on the methyl group with the 20 min positron emitter carbon 11. Fifteen to 25 mCi corresponding to 15–30 nmol were injected i.v. and sequential tomographic pictures of the brain were obtained. In some experiments, therapeutic doses of various benzodiazepines were injected i.v. subsequently in order to study the displacement of the radioactive ligand from brain structures. Lorazepam was shown to displace [11C]flunitrazepam from brain tissue, although other benzodiazepines (chlordiazepoxide, Ro 116896 and Ro 116893) led to a redistribution of the radioactive ligand in the body accompanied by an increase of brain radioactivity.

A method for labeling MQNB (Methiodide quinuclidinyl benzilate) with carbon-11 using11C-methyl iodide is reported. Injectable labeled product (100 mCi; max. 200 mCi) radiochemically and chemically pure is obtained in a 30 minute synthesis time with a specific activity of 1 Ci/μmol, (max. 2.3 Ci/μmol).

In order to study “in vivo” the brain specific receptor sites of benzodiazepines, a method for carbon-11 labelling of diazepam and flunitrazepam without irradiation risk to personnel is described. 70 mCi (max. 140 mCi) of injectable labelled product, chemically and radiochemically pure, are obtained in 45 minutes with a specific activity of 810 Ci/m mole.