Carbon-11, often denoted as 11C, is a radioactive isotope of carbon. It is a positron-emitting radionuclide with a half-life of approximately 20.364 minutes. Carbon-11 is commonly used in positron emission tomography (PET) imaging due to its short half-life, which allows for real-time monitoring of biological processes in living organisms.
Carbon-11 is produced by bombarding a target material, typically nitrogen gas, with high-energy protons in a cyclotron. The resulting nuclear reaction produces Carbon-11, which can then be incorporated into biologically active molecules such as glucose, dopamine, or amino acids. These radiolabeled compounds can be injected into the body, where they accumulate in specific tissues or organs. The emitted positrons from the Carbon-11 decay interact with electrons in the tissue, leading to the emission of gamma rays in opposite directions. These gamma rays are detected by the PET scanner, allowing for the reconstruction of images that reflect the distribution of the radiotracer in the body.
The use of Carbon-11 in PET imaging enables researchers and clinicians to visualize metabolic processes, receptor binding, and other physiological functions at the molecular level. This information is valuable for diagnosing diseases, monitoring treatment responses, and advancing our understanding of various biological processes.
Overall, Carbon-11 plays a crucial role in molecular imaging and has significantly contributed to the field of nuclear medicine by providing non-invasive and quantitative insights into the functioning of living systems.
Properties:
11C is a positron emitter (β+ 99.8%) at 960 keV (maximum range 4.1mm – average positron energy at 386 keV) with a short half-life of 20.4 min decaying into stable Boron-11 (11B). This gamma emission is followed by annihilation producing two gamma rays at 511 keV. 11C also shows 0.2% decay by electron capture. This short half-life is however, sufficient for allowing its transformation into a reactive organic chemistry building block (11CO, 11CO2, 11CH3I, …) which allows quick incorporation of radioactive carbon in tracers.
Manufacturing:
11C is usually produced in a low-energy cyclotron (3–20 MeV) by irradiation with a proton beam of a nitrogen-14 target (natural abundance 99.6%) via the reaction [14N(p,α)11C] (peak at 7-8 MeV). Depending upon the irradiation conditions (most often presence of oxygen), 11C is obtained in the form of carbon dioxide (11CO2) which is either immediately introduced in a final tracer or transformed into a reactive species that can be purified and used in the next chemical step.
11C can also be produced at energies below 5 MeV via the [11B(p,n)11C] nuclear reaction and up to 250 mCi of 11C can be expected based on a 30 min irradiation at a beam current of 100 µA. However, this route is much less favorable and more difficult to implement than the (p,α) route based on 14N.
Source and availability:
Any owner of a cyclotron, and even a low-energy cyclotron, is able to produce 11C. Usually, all research institute- and hospital-installed cyclotrons are equipped with the targets and the laboratories able to produce 11C-labeled tracers. Of course, a team of radiochemists is needed on-site.
Derivatives:
Carbon is the second most common atom in organic molecules after hydrogen and therefore, a radioactive carbon atom can play an important role in the elucidation of biological mechanisms. No hydrogen radioisotope has a half-life that fits with the clinical requirements (3H-Tritium has a half-life of 12.33 years which is too long for clinical use), so any molecule labeled with a radioactive carbon atom could play an important role in the description and follow up of the biological cell mechanisms. Unfortunately, the two carbon radioisotopes that may be useful have either a too long half-life (14C, 5,730 years, which forbids use in humans) or a too short half-life (11C, 20min, which limits industrial applications).
As a consequence, 11C must be considered mainly as a R&D tool (see Table 46:Nonexhaustive list of 11C-labeled tracers used at some R&D sites), and derivatives are produced and used locally (hospital). Only one 11C-derivative (11C-Choline) obtained a marketing authorization, first from at the Mayo Clinic, Rochester MN, USA. The company
IBA Molecular NA filed an ANDA which was approved by end of 2015.
Price:
The price of 11C has no meaning per se as it can be shipped only in a very limited area and needs to be transformed immediately into a labeled tracer. Each dose of an 11Clabeled compound needs to be manufactured individually or for a maximum of two patients. The overall cost of one of these doses depends upon the time of irradiation and synthesis (during which a full-time radiochemist, a part-time analyst and a part-time radiopharmacist are needed), the price of the cold kit and the value of amortization. Such a dose would cost presently between EUR 400 and EUR 1,500 (US$ 520–1,950). As a reference, in the USA, 11C-Choline was charged (and reimbursed) at a level of US$ 5,000 per patient during the first two years post launch.
Issues:
◼ Short half-life radionuclide which limits applications to clinical research purposes.
◼ 11C and 11C-labeled molecules can be shipped only over very limited distances.
◼ Several chemical routes have been developed to label molecules. 11C radiochemistry is not an issue anymore.
◼ Marketing an 11C-tracer would suppose that the market (i.e., each hospital) has access to at least a baby cyclotron. This huge investment and the maximum number of doses that could be produced daily per center (realistically below five) bring any business plan beyond profitability.
◼ Industrialization is realistic only as long as reimbursement at high level is guaranteed and makes sense in the frame of a local business plan for a tracer in which not too much development investment is needed (generic, grandfathered).
Comments:
11C is the best PET radionuclide for research purposes. It is the only atom that can be integrated into any biological organic molecule without disturbing its biological behavior. Its chemistry allows applications in the development of pharmaceuticals. 14C has a far too long half-life to be used for medical applications. Unfortunately, the short half-life of 11C precludes use in radiopharmaceuticals with larger marketing authorization. For this reason, 11C-labeled molecules, even those used regularly in R&D in humans, are reported in this document only in the Pharmacological tool section of Volume 3. Unless the regulations change, it will remain difficult to obtain marketing authorizations for molecules labeled with this radionuclide. 11C-Choline is the exception that shows that the interest is really only local. Also, as a consequence of the short half-life, a radiochemist can produce only the amount of tracer required for one to three patients (providing there are three cameras available in parallel). For the time being the price per dose will stay at quite high levels as the synthesis needs to be repeated for each patient or very small batch.
In a recent new business model under evaluation, it was concluded that an isolated center dedicated to 11C-labeled molecules could be profitable providing there is a guarantee (agreement with the nearby medical center) that all doses that are produced daily are sold. Such a model could be based on an on-demand 11C-labeling process and must be organized around screening of patients that will have to travel to the imaging site. There will be no need for a global MA for such molecules but a way for reimbursement must be found on a case-by-case basis. It is the model put in place for 11C-Choline at the Mayo clinic which is its own customer.
Numerous molecules have been labeled with 11C and some companies are developing specific kits for this chemistry. The most interesting 18F-labeled molecules have been derived from their 11C-equivalents.
Some companies (e.g., CEA/Lotus Project) are developing tools (a dedicated cyclotron with synthesis automate and direct syringe preparation of ready to use 11C-labeled tracers). However, even if their system could be fully automated, they are not aiming at competing with large-scale manufacturing and these companies target only research and development applications (preparation of unit doses for clinical trials).