Pet Scanning

Positron Emission Tomography

Sarah M. Don

Chemistry ERT Semester 4, 2008 Dr Stolarchuk

October 31, 2008

© Sarah Don, Australia, 2008

Positron Emission Tomography (PET) is a type of diagnostic imaging that is used to identify tumourous growth in specific types of tissue. Depending on the tissue of interest different tracers may be used, however the most common radioisotopic tracer is 2-fluoro-2-deoxy-D-glucose (FDG). This extended response task specifically looks at how PET scanning works and its role in the diagnosis of lymphomas. Fluorine-18 is manufactured in a cyclotron by bombarding oxygen-18 with protons to cause a proton-neutron spallation. (see Equation 1) This is a possible equation showing that when a proton collides with an O18 nucleus, F18 is produced and a neutron is released (notice that the number of protons and nucleons are equal on both sides of the equation. 18 8𝑂

+ +11𝑝 →

18 9𝐹

+ 10𝑛

Equation 1

When the fluorine-18 in FDG decays, it throws a positron out of the nucleus to return to O18 which is stable. (see Equation 2) This positron soon collides with an electron and is annihilated, releasing resultant gamma rays. (see Equation 3) These gamma rays are released approximately 180° to each other, allowing the gamma camera inside the PET gentry to trace the annihilation back to the tissue it originated from. 18 9𝐹

→

0 +1𝛽

Figure 1 – Molecular diagram of 2fluoro-2-deoxy-D-glucose.

18 8𝑂

+ +10𝛽

+ −10𝛽 → 𝛾

Equation 2 Equation 3

The F18 is then bound to glucose molecules to form 2-fluoro-2deoxy-D-glucose. (see Figure 1) Fluorine-18 is able to replace hydroxyl groups on the deoxyglucose molecule because it has similar polarity. This molecule acts just like any other form of glucose in the body and thus can be used as a tracer. However, it is still not exactly the same as a hydroxyl group and this could possibly cause biochemical problems where the glucose would normally be absorbed by tissues if the hydroxyl groups were not replaced with F18 atoms. However there has not yet been a lot of research in this area.

The process of performing a PET scan involves injecting the patient with FDG and then tracing where the FDG is most concentrated. Approximately 20 minutes after the patient has been injected with FDG, they lay horizontally and travel very slowly through the PET scanner’s gamma camera gantry (the donut-shaped section). F18 has a half-life of 110 minutes, so technicians have to work quickly to transport the F18 from the cyclotron to the hospital/PET clinic and perform the PET scan. The resulting 3D computerised model of the patient is generated by positron emission tomography – registering the resultant gamma rays of electron-positron annihilations from decay where the FDG has accumulated in the body. Malignant types of lymphoma have a very fast metabolism and absorb more glucose faster than other tissues. When FDG is injected into the patient and a PET scan is performed, the areas that absorb the most FDG show up darker on the computer-generated image. This shows very accurately the areas of tumourous growth. In Figure 2a, the arrows point to areas of lymphoma, illustrated by darker areas. Figure 2b shows another scan of the same patient after they had received treatment. The previously darker areas now show up lighter. The brain, bladder and kidneys always show up darker because they absorb (or contain) more glucose than other organs, which makes PET scanning unsuitable for the identification of malignancies in these areas.

© Sarah Don, Australia, 2008

Many people fear the concept of being injected with radioactive material. This is mostly due to misinformation and lack of education in the area of nuclear diagnostic imaging. Because of the mysteriousness of radioactivity, some people choose not to have the PET scanning that could potentially diagnose a lymphoma in its early stages which would allow them to start treatment that could save their life. Fluorine-18 has a relatively short half-life of 110 minutes. This means that after 110 minutes, only half of the original radioactive material (F18) remains while Figure 2 – a) Scan used to diagnose patient with malignant the other half has decayed to stable O18. lymphoma; b) scan of patient after treatment showing the Also, glucose is naturally excreted in urine elimination of the lymphoma (AI, 2008) and so after about 24hrs, almost all the F18 has decayed or been excreted. (RxList, 2008) The amount of radiation the patient receives from one injection of FDG is little more than a single x-ray. Although PET scanning is not useful for the detection of lymphomas in the brain, bladder and kidneys, it is 95% accurate for other tissues in the body (Chengazi, 2003). PET scanning can detect a lymphoma before any other type of scanning can. This is because scans such as MRI (magnetic Resonance Imaging), x-rays and CT (Computed Tomography) scans look at tissue shape and density in order to identify abnormalities. PET is a scan of chemical abnormalities – where glucose is being absorbed most due to the high metabolism of a malignancy – so a lymphoma can be detected even when it is only made up of several cells. CT scanning involved a series of x-rays that form a computerised 3D model of the body. Before the scan, the patient is injected with iodine which acts as a contrast agent (to make it easier to distinguish between tissues). (Rapkins, 2004) Over the course of one CT scan, the patient experiences approximately 300 times the radiation of a single x-ray. Because CT scans only show macroscopically physical deformities and growths, in order to identify a tumour’s nature (malignant or benign) a biopsy has to be taken and pathologically analysed. This increases risk of infection as well as causes discomfort to the patient. Also, lymph nodes can become swollen due to viral and bacterial infection, and so detection of a lymphoma exclusively by its shape and density is not accurate. Gallium-67 scintigraphy (another nuclear imaging technique) works similarly to PET, however zinc-68 is bombarded with protons to produce G67 (see Equation 4) and the gamma rays are possibly produced by the emission of an electron to form stable Zn67. (see Equation 5) 68 30 𝑍𝑛

+ +11𝑝 →

67 31 𝐺𝑎

Equation 4

67 31 𝐺𝑎

0 −1𝛽

67 30 𝑍𝑛

Equation 5

+

→

Ga67 binds to proteins in place of iron molecules due to its ferric-like chemical and physical properties. With a half-life of 72 hours, Ga67 stays in the body much longer than F18 from a PET scan. (Mauch, 2003) This increases the risk of tissue damage due to radiation and prevents the patient from interacting with other people too closely for a number of days. Also, Ga67 must be injected 2448hrs before the scan, and because the Ga67 binds to proteins, as opposed to glucose, it is not as suited to identifying malignant lymphoma as PET scanning is. This type of scanning is not suitable for

© Sarah Don, Australia, 2008

staging and restaging lymphoma during and after treatment as residual chemotherapy can interfere with the imaging more so than with PET. PET imaging is able to identify malignancies even before they become macroscopically visible, and also assist the tracing of where any cancerous cells have spread around the patient’s entire lymphatic system. Although the patient receives a small amount of radiation, the benefits of receiving the diagnostic scans far outweigh any biological damage that may be caused by the radiation from FDG.

Bibliography Alliance Imaging (2008) Lymphomas: Case Study, PET Alliance Imaging, http://www.petforcancer.com/lymphomas/casestudies/case_01.html (27/10/08) V. Chengazi, J.W. Friedberg (2003) “PET Scans in the Staging of Lymphoma: Current Status”, The Oncologist, Vol.8, p.438-447. 67

P.M. Mauch (2003) Non-Hodgkin's Lymphomas: A Self-Study Program, Ga Citrate Imaging, Lippincott Williams & Wilkins, USA. G. Rapkins et al. (2004) Medical Physics, New Century Senior Physics: Concepts in Context, Oxford University Press, Singapore. RxList (2008) Fludeoxyglucose F-18 Injection – Drug Description, RxList Inc. http://www.rxlist.com/fludeoxyglucose-drug.htm (29/10/08)

© Sarah Don, Australia, 2008