Chemistry Reference
In-Depth Information
carbon-11, nItrogen-13, and oxygen-15
chemIstry: an IntroductIon to chemIstry
wIth short-LIved radIoIsotopes
Philip W. Miller
Department of Chemistry, Imperial College London, London, UK
Koichi Kato
Department of Molecular Imaging, National Centre of Neurology and Psychiatry, Kodaira, Tokyo, Japan
Bengt Långström
Department of Biochemistry and Organic Chemistry, Uppsala University, Uppsala, Sweden
Neuropsychopharmacology Unit, Centre for Pharmacology and Therapeutics, Division of Experimental Medicine,
Imperial College London, London, UK
Department of Nuclear Medicine, PET & Cyclotron Unit, Odense University Hospital, University of Southern
Denmark, Institute of Clinical Research, Odense, Denmark
4.1
IntroductIon
Carbon-11, nitrogen-13, and oxygen-15, with their respective half-lives of 20.4, 10.0, and 2.0 min., present significant chemical
challenges for the production of tracer molecules for PET imaging [1-3]. Despite their short half-lives all three isotopes are
important and versatile isotopes for the synthesis of PET tracers. The presence of stable carbon-12, nitrogen-14, and oxygen-16
in natural products and drug compounds make the corresponding PET isotopes obvious choices for the preparation of
equivalent labelled compounds that would display virtually identical chemical and biological behaviour. Although the half-
lives of these PET isotopes preclude time-consuming multistep syntheses, a range of clever radiochemistry has been developed
over many years for introducing these isotopes into tracer molecules. Of these isotopes, C-11 has received the most attention
owing to its longer half-life, which enables a wider range of chemical transformations, and access to more diverse chemical
structures. N-13 and O-15, in comparison, are typically used to prepare simple molecules such as
13
NH
3
,
15
O
2
, and [
15
O]H
2
O.
The aim of this chapter is twofold, first to introduce the field of C-11, N-13, and O-15 chemistry to the reader who may be new
to the field, and second, to provide an up-to-date account of their chemistry for those who are more familiar with the field. The
application of radiolabelled tracers prepared from these isotopes will not be discussed in much detail.
There are many challenges facing the chemist in the preparation of PET tracers using short-lived isotopes. Time is the most
obvious parameter and places severe limits on the possible types of chemistry. A general rule of two to three half-lives is loosely
applied to PET tracer synthesis from the end of cyclotron bombardment (EOB). For example, the production of an O-15 labelled
compound would have to be complete within a short 6 min. 'window' to ensure a viable production method. For C-11 labelling
protocols, a typical 40 min. reaction window will generally permit a maximum of only two or three discrete chemical transfor-
mations. Consequently, much of the chemistry development for synthesis with short-lived isotopes is centred on the preparation
of simple and reactive precursor molecules for the introduction of the isotope quickly and typically within one chemical step.
