**1. Introduction**

Carbon-11 (11С) is an artificial radioisotope of carbon. Crane and Lauristen made the production of this short-lived radionuclide and investigated its physical properties in 1934 [1]. They demonstrated that carbon-11 decays by positron emission to the stable nuclide 11B [Eq. (1)]. Due to its favorable decay characteristics (t1/2 = 20.33 min, 98.1% by β<sup>+</sup> emission, 0.19% by electron capture), carbon-11 was considered as a useful labeling tool for medical purposes. The first biological application of carbon-11 was published by Ruben in 1939 who investigated photosynthesis in plants using [11C]carbon dioxide [2]. The potential of 11C-labeled compounds for non-invasive probing of physiological and biochemical processes in humans was subsequently realized [3]. The first carbon-11 experiment on humans was performed by Tobias in 1945 who studied the fixation of [11C]carbon monoxide by red blood cells [4]. However, the use of carbon-11 was

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons

limited in next 20 years [5]. This delay was a consequence of easy access to reactor-produced carbon-14 from the 1950s, which superseded the use of cyclotron-produced carbon-11. Until late 1950s, the concepts of emission and transmission tomography were introduced by David Kuhl and Roy Edwards. The interest in carbon-11 was renewed and the application of carbon-11 was extended in 1960s.

$$\begin{aligned} \text{the interest in carbon-11 was removed and the application of carbon-11 is} \\\\ \text{ $^{11}$ C} \rightarrow ^{11}\text{B} + \text{ $^{3}$ +} + \text{v}\_{\text{e}} + 0.96 \text{ MeV} & \quad 98.1\% \\\\ \text{ $^{11}$ C} + \text{ $^{1}$ e} \rightarrow ^{11}\text{B} + \text{v}\_{\text{e}} + 1.98 \text{ MeV} & 0.19\% \end{aligned} \tag{1}$$

resonance imaging (MRI). The fusion offers more precise images with accurate functional assessment from PET and anatomical information form CT or MRI. Applications of PET in oncology [8–12], neurology [13–16], psychiatry [17–19], cardiology [20, 21] and other medical

The use of PET relies on the availability of appropriately labeled radiopharmaceuticals. Carbon-11 is one of the most useful radionuclides for PET chemistry, since the carbon is present in any organic molecule so that the introduction of carbon-11 in a molecule does not modify the properties of this molecule. In addition, the short half-life of carbon-11 allows for l consecutive *in vivo* studies with injections of various radiotracers in the same subject on the same day. The pioneering work in the area of radiochemistry at the Washington University in 1960s demonstrated the great potential of 11C-labeled compounds in biological sciences [5].

sively used as a starting point for the synthesis of different kinds of 11C-labeled compounds [26–28]. With the increasing demand of radiotracers and continuous developments of organic chemistry, a number of methodologies have been developed in recent years to enhance production of 11C-radiotracers both from a technical and chemical point of view. However, [11C] carbon dioxide is still the most common and versatile primary labeling precursor in the production of 11C-labeled radiopharmaceuticals. This chapter focus on the use of [11C]carbon

Several nuclear reactions can be used to produce carbon-11 [29, 30]. Among these processes the <sup>14</sup>N(p,α)11C nuclear reaction is by far the most convenient and most commonly used method

dioxide as the starting point for radiolabeling PET radiopharmaceuticals (**Scheme 1**).

) made it possible to be exten-

specialties [22–24] became one of the fastest growing area in radiology [25].

The simple cyclotron production of [11C]carbon dioxide (11CO2

**Scheme 1.** Representative transformations in [11C]carbon dioxide radiochemistry.

[

11C]Carbon Dioxide: Starting Point for Labeling PET Radiopharmaceuticals

http://dx.doi.org/10.5772/intechopen.72313

125

**2. Carbon-11 chemistry**

**2.1. Cyclotron: generation of carbon-11**

Decay of carbon-11 by positron emission or electron capture.

Positron emission tomography (PET) is a type of functional molecular imaging technique using probes, known as radiotracers, consisting of bioactive molecules tagged with positronemitting radionuclides [6]. As carbon-11 undergoes positron emission decay, it emits a positron. The positron travels a short distance in the surrounding tissue until it collides with an electron. The annihilation produces a pair of gamma rays, which are emitted simultaneously in nearly opposite directions with energy of 511 keV each. The photons can be detected by pairs of collinearly aligned detectors in coincidence. The detectors of a PET system are installed in a ring-like pattern, which allows measurement of radioactivity through the organ of interesting at large angles and radial distances. The three-dimensional images can be generated by reconstruction (**Figure 1**). The ability to image and monitor molecular events *in vivo* and in real time is of great value for unveiling a detailed picture of fundamental biochemical and physiological processes in living organisms [7]. Information about metabolism, receptor/ enzyme function, and biochemical mechanisms in living subjects can be obtained directly from PET imaging studies. The recent development of hybrid instrument combines functional PET with an anatomical modality such as computerized tomography (CT) or magnetic

**Figure 1.** The principle behind PET imaging: (a) the injection of radiopharmaceuticals; (b) positron travels a short distance and collides with an electron, then two 511 keV gamma rays emit simultaneously at approximately 180° to each other after annihilation; (c) system detects gamma rays and then generates three-dimensional images.

**Scheme 1.** Representative transformations in [11C]carbon dioxide radiochemistry.

resonance imaging (MRI). The fusion offers more precise images with accurate functional assessment from PET and anatomical information form CT or MRI. Applications of PET in oncology [8–12], neurology [13–16], psychiatry [17–19], cardiology [20, 21] and other medical specialties [22–24] became one of the fastest growing area in radiology [25].

The use of PET relies on the availability of appropriately labeled radiopharmaceuticals. Carbon-11 is one of the most useful radionuclides for PET chemistry, since the carbon is present in any organic molecule so that the introduction of carbon-11 in a molecule does not modify the properties of this molecule. In addition, the short half-life of carbon-11 allows for l consecutive *in vivo* studies with injections of various radiotracers in the same subject on the same day. The pioneering work in the area of radiochemistry at the Washington University in 1960s demonstrated the great potential of 11C-labeled compounds in biological sciences [5]. The simple cyclotron production of [11C]carbon dioxide (11CO2 ) made it possible to be extensively used as a starting point for the synthesis of different kinds of 11C-labeled compounds [26–28]. With the increasing demand of radiotracers and continuous developments of organic chemistry, a number of methodologies have been developed in recent years to enhance production of 11C-radiotracers both from a technical and chemical point of view. However, [11C] carbon dioxide is still the most common and versatile primary labeling precursor in the production of 11C-labeled radiopharmaceuticals. This chapter focus on the use of [11C]carbon dioxide as the starting point for radiolabeling PET radiopharmaceuticals (**Scheme 1**).
