Chemistry Reference
In-Depth Information
Although the time issues and safe handling of short-lived radioactive PET isotopes may be obvious, there are added
difficulties when dealing with the extremely small mass of radioisotopes produced. Typical reactions with PET isotopes
are performed on the picomolar to nanomolar scale. reacting and processing such small amounts of material have led to
the development of miniaturised reaction systems and integration of microfluidic technology for radiolabelling reactions.
Additionally, these very low amounts of radioisotopes result in a stoichiometric imbalance with the 'cold' reagent precur-
sors with which they are reacting. The vast stoichiometric excess (~1 × 10
3
- 1 × 10
5
fold) of cold precursor results in
pseudo-first-order reaction kinetics with respect to the radioisotope concentration. This, in fact, can be advantageous for
certain reactions and result in an acceleration of the labelling process; however, such excess reagents may be difficult to
remove during the purification process. The efficiency of a labelling process is judged by both its radiochemical yield
(rCy) and specific activity (sA) of the final labelled compound. rCy is a function of both the chemical yield and
half-life of the radioisotope and is expressed as a fraction of the radioactivity present after a radiochemical separation.
rCy is quoted as being either decay corrected, taking into account the radioactive decay that occurred between two
different times, and non-decay corrected, which does not account for radioactive decay. High rCys, although desirable,
are not always essential for a viable tracer production. The specific activity is a measure of the radioactivity per unit mass
of the labelled compound and is commonly expressed as gBq/μmol or Ci/μmol. inevitably, some isotopic dilution with
the naturally occurring isotope occurs during the labelling process, which means that theoretical sA maxima are never
reached even for carrier-free methods. specific activities are much lower for carrier-added synthesis methods, such as
those used for the production of
18
F[F
2
] in electrophilic fluorinations (see Chapter 3), to due to a direct result of isotopic
dilution from the added carrier. specific activities of PET-labelled products are typically in the order of 50-500 gBq/μmol
(~1-15 Ci/μmol), are generally required to give a good quality PET data.
4.2
carbon-11 chemIstry
The carbon-11 isotope is most widely produced by the proton bombardment of nitrogen-14 (
14
N(
p,α
)
11
C) in a gas phase
cyclotron target.
11
CO
2
and
11
CH
4
are the two most commonly used
11
C 'primary' precursors and are formed when a small
percentage of either oxygen or hydrogen is present in the target gases. The vast majority of
11
C labelled PET tracers are made
from these two simple precursors; consequently, there is considerable effort placed into converting
11
CO
2
and
11
CH
4
into
more reactive molecules for labelling. scheme 4.1 summarises some of the major reactive 'secondary' precursors that are
derived from
11
CO
2
and
11
CH
4.
11
CH
2
O
11
CS
2
11
CH
3
OTf
11
CH
3
OH
11
CH
3
I
11
CH
3
NO
2
11
CO
2
11
CH
4
11
CO
11
CCl
4
11
COCl
2
[carbonyl
-11
C]RCOCl
[
11
C]HCN
[carbonyl
-11
C]RCOOMX
[
11
C]RCH
2
X
[
11
C]RCH
2
OH
scheme 4.1
The major
11
C-precursors used in the synthesis of
11
C-labelled compounds produced from either
11
CO
2
or
11
CH
4
.
