l-[3-11C]Serine has been prepared from [11C]methanol by a series of coupled enzymatic reactions using alcoholoxidase (EC 1.1.3.13) and catalase (EC 1.11.1.6) to give [11C]formaldehyde, which was condensed with tetrahydrofolate. The N5, N10[11C]methylenetetrahydrofolate formed, was used directly with serine hydroxymethyltransferase (EC 2.1.2.1) immobilized on glutaraldehyde-activated controlled porous glass beads. l-[3-11C]Serine (specific radioactivity 30–50 mCi/μmol) was obtained in a 1–2% yield after a synthesis time of 50–65 min counted from release of [11C]carbon dioxide.

The kinetics of 11C-labelled morphine and pethidine were studied by positron emission tomography (PET) at different levels of the spinal canal (C4, T4, T5, T6, L1 and L6). Studies were performed in the Rhesus monkey after intrathecal and extradural administration of the drugs at the lumbar level (L3-L4 or L4-L5, seven experiments). Radioactivity 100-300 times higher than with even distribution in the body was measured initially near the site of injection for both morphine and pethidine, irrespective of the route of administration. After injection of pethidine, high activity was observed at the L6 and L1 levels, whilst the radioactive uptake was lower at T6 (10-20% of those at lumbar level). Morphine-derived 11C-radioactivity showed more constant levels along the spinal canal, except at C4 where radioactivity was low. In CSF taken from the cervical level the peaks of radioactivity of the two drugs appeared 80-170 min after injection. The importance of different distribution routes was quantified in a pharmacokinetic compartment model, using the above results. The systemic distribution was extensive, irrespective of drug or route of administration. From the site of injection the systemic distribution was at least 60 times larger than the rostral distribution within the spinal canal.

This report describes the synthesis of L- and D-[methyl-11C]methionine in pure enantiomeric forms. The compounds were prepared routinely approximately 1,000 times with less than 20 failures. Starting with carbon-11 (11C) methyl iodide, a simple one-carbon precursor produced from a one-pot or a two-pot apparatus, L- and D-[methyl-11C]methionine were prepared, respectively, with an optical purity higher than 99% in 40%-90% radiochemical yields. The total time for synthesis, starting from [11C]carbon dioxide, was 12-15 min. The crude product usually had a radiochemical purity greater than 95%. The total time for synthesis, including LC purification, was 20-30 min. The radiochemical purity of the product in each case was greater than 98%.

Prostaglandins (PG) are endogenous compounds that have been extensively studied by various techniques. In this paper, the syntheses of methyl esters of PGD2 and PGE2, labelled with 11C for PET investigations, are reported. The prostaglandin was esterified via its carboxylate anion, with [11C]methyl iodide as alkylating reagent, in a dimethyl sulphoxide-dimethylformamide mixture. To minimize the base-catalysed degradations, the carboxylate anion was generated in situ by use of tetramethylpiperidine. The radiochemical yield, including purification, was 70%, with a total synthesis time of 20-25 min counted from the end of the [11C]methyl iodide synthesis.

New 11C-labelled precursors [1-11C]ethyl, [1-11C]propyl, [1-11C]butyl, and [1-11C]isobutyl iodides have been prepared by a 3-step reaction route using a one-pot system. The labelled iodides were obtained in 20–55% radiochemical yields and 65–95% radiochemical purities, with a total time for synthesis of the order of 10–14 min. The labelled iodides have been used in alkylation reactions with nitrogen, oxygen and carbon nucleophiles. The nitrogen alkylation reactions are exemplified by the synthesis of the analgetics N-[1-11C-ethyl]lidocaine and N-[1-11C-butyl]bupivacaine. The synthesis of 3-nitrophenyl[1-11C]propyl ether is also presented in this paper as an example of an oxygen alkylation.

Our knowledge of the pharmacokinetics of analgesics and antimigraine drugs in cranial structures is incomplete. This is mainly due to the difficulties of sampling blood or tissue from the region in question. However, the development of positron emission tomography (PET) has made it possible to obtain cross-sectional images of the distribution of 11C-labeled drugs and metabolites in the living animal. PET studies with 11C-labeled drugs make dynamic quantitative in vivo autoradiography of the head possible.

The regional uptake in the brain of Rhesus monkeys of i.v. administered 11C-labeled morphine, codeine, heroin and pethidine was studied by means of positron emission tomography. The technique measures the sum of parent drug and radiolabeled metabolites. (For the sake of simplicity the drug derived radioactivity is denoted by the drug name.) Morphine had a limited uptake to discrete areas of the brain. The maximum normalized uptake, with respect to dose per kilogram body weight, was about 0.2, i.e., 20% of the calculated activity if the drug had been evenly distributed throughout the body of the monkey. Maximum radioactivity appeared 30 to 45 min after injection. Morphine left the brain slowly with an estimated half-life of more than 2 hr. An area with a normalized uptake of about 1.0 was detected centrally in the lowest horizontal transsection of the skull. The origin of this area was identified as the pituitary. Codeine, heroin and pethidine were taken up to the brain to a larger extent than morphine, with maximum normalized uptakes of 2.6, 4.6 and 6.3, respectively. Maximum radioactivities of these drugs were achieved earlier and the elimination rates were faster than for morphine. Differences in the uptake of these drugs to the brain, as well as differences in time to maximal normalized uptake and rate of disappearance are considered to reflect differences in the lipophilic character between the drugs. Pethidine had the most rapid and extensive uptake followed by heroin, codeine and morphine in order of decreasing lipophilicity.