Labelling of aromatic compounds with carbon-11

The rapid development of life sciences connected with biochemical investigations of living processes initiated the research for labelling organic compounds during the fifties of the 20^th century. The need for inserting radioactive carbon-14 atoms into aromatic rings became a matter of interest as more than 50% of naturally occurring and biologically active compounds contain benzenoid and heteroaromatic rings. The radionuclide of choice for labelling was ¹⁴C in many cases due to the need for stable isotopic labelling. A number of useful labelling methods was developed.

For reflecting in vivo processes in man and animal the radionuclide of choice changed: the positron emitter carbon-11 became of interest since the external measurement of biochemical processes using Positron Emission Tomography was developed.
The labelling procedures of carbon-14 radiochemistry could not be transferred to carbon-11 chemistry due to the different radionuclide and radiochemical properties as short half life, low substance amounts and high doses rates. New labelling methods for syntheses of ¹¹C-labelled compounds had to be developed.
Initial investigations from 1982 for ¹¹C-labelling of aromatic compounds were unsatisfactory. First in our systematic work a number of suitable labelling syntheses were developed for carbon-11 introduction into benzenoid and heteroaromatic rings (Figure 1, Steinbach at al. J. Labelled Cpd. Radiopharm., 36 (1995) 33-41, Mäding et al. J. Labelled Cpd. Radiopharm., 41 (1998) 647-656, Zessin et al. J. Labelled Cpd. Radiopharm., 42 (1999) 725-736). The labelling position was determined by ¹¹C/¹³C co-labelling experiments and appropriate ¹³C-NMR investigations for the reaction path 1 and 2.

Not all derivatives of choice are available by this synthetic routes so far. An overall view will be given and the chances and limitations of this methods will be discussed.