16.7: 18-F fluorodeoxyglucose and Atherosclerotic Plaque

This is a final project completed by Janet Jimenez for Chemistry 150 in Fall 2021 at Modesto Junior College. When citing this project, she is the author.

[ ¹⁸F] fluorodeoxyglucose and Atherosclerotic Plaque

Radioactive elements are known to be dangerous and deadly, but what if I told you that they could also save lives. Ironic, right? By using the appropriate amount and proper handling, radioactive elements are of great help when trying to detect life threatening diseases in humans. An example is the positron emission tomography (PET) scan. The PET scan is one of few imaging techniques offered within the medical community that allow health care providers to see any abnormalities within the patient’s body. All of this is possible because of a radioactive drug: Fluorodeoxyglucose. In this final project, we will see how chemistry is an active participant in nuclear medicine, and how the PET scan came to be. This project will primarily focus on how the PET scan is used to detect atherosclerotic plaque inflammation, something that was not thought of doing before.

            The PET scan has been used by many health care providers to detect early signs of cancer, brain disorders, and heart disease. The way the PET scan works is by the use of a radioactive tracer called [ ¹⁸F] fluorodeoxyglucose (Figure 1). If we take a closer look at its composition we see that it is made of C₆H₁₁¹⁸FO₅. The carbon, hydrogen, and oxygen seem to look “normal” in the molecular formula, except for Fluorine. This is because the Fluorine represented in the molecular formula and in Figure 1, is an isotope of Fluorine (a radioactive one).

Figure 1 (National Center for Biotechnology Information)

However, to achieve the “stable” molecular compound listed in Figure 1, it must be synthesized. Figure 2 demonstrates how it is possible to achieve [ ¹⁸F] fluorodeoxyglucose. Through a series of rearrangements, and the addition of acid and bases, the final product is formed. This product is now safe for humans use.

 

Figure 2 (Review of 18F-FDG Synthesis and Quality Control)

 

So now keeping the pictures above in mind, we now wonder, how does [ ¹⁸F] fluorodeoxyglucose (¹⁸FDG) interact with the human body? Well first you have to begin by knowing how it is introduced into the body. A very small amount of this radioactive substance is injected into the body. The body is then given some time to process this substance. From this point on, it is where the chemistry begins. “[¹⁸F]-fluorodeoxyglucose (¹⁸FDG) is a glucose analogue that is taken up by cells in proportion to their metabolic activity” (Rudd, 2002). Because of ¹⁸FDG ‘s composition, cells are able to interact with it. “FDG is facilitated by the relatively long half-life of the ¹⁸F isotope (109 min), which allows for tracer transport and typical whole body imaging… [it] is [then] transported from the plasma into cells... [where] FDG is phosphorylated, preventing its return to the circulation. At this point FDG is trapped within the cell and is not metabolized further” (Rudroff, 2014). Think of ¹⁸FDG as a glowing donut; cells that have a lot of appetite (insatiable) will eat ¹⁸FDG faster than those that are satiable. Now, the radioactive tracer has moved through your bloodstream, finding its way through the body, interacted with cells, and now has to display it has found its target (Figure 3).

 

 

Figure 3

 

¹⁸FDG has now made its way into an area (carotid artery) where there are a lot of insatiable cells. So, now there is a focused amount of ¹⁸FDG at the carotid artery. It is here that the radioactive tracer begins detecting for atherosclerotic plaque inflammation in the cells. As it detects the metabolic activity of the cells, an image is now displayed. This image then shows the area of interest.

 

The bright contrast is the metabolic activity of the cells around the plaque in the carotid artery. It was seen that there was a “high ¹⁸FDG uptake in the brain, jaw muscles, and facial soft tissues” (Rudd, 2002). Thus, showing that a PET scan is able to detect the cells of interest.

            When comparing individually the PET scan and the CT, the PET scan shows a more focalized view of the affected area. “The lower row (from left to right) demonstrates a low level of ¹⁸FDG uptake in an asymptomatic carotid stenosis. The black arrow highlights the stenosis on the CT angiogram, and the white arrows demonstrate minimal ¹⁸FDG accumulation at this site on the ¹⁸FDG-PET and co-registered PET/CT images” (Rudd, 2002).

            Throughout this project, radioactive tracers are explained and show how their involvement in nuclear medicine is crucial. Specifically the role of radioactive tracers in detecting atherosclerotic plaque inflammation. [¹⁸F] fluorodeoxyglucose was shown to be an effective radioactive tracer and a more competent method of imaging in comparison to other imaging programs/ procedures. It is through the understanding and application of chemical properties that we are able to further advance within medicine. As we know, science is constantly evolving, chemistry is constantly evolving. We have advanced in ways we would have never imagined 50 years ago. So who knows, there just might be other effective ways of seeing/ prescreening for diseases that we have yet to discover.

Learning Questions:

1.      What is an isotope? (Hint: you can find more information on isotopes in section 3.5 of the book)

2.      Why is the radioactive tracer [¹⁸F]-Fluorodeoxyglucose effective?

3.      Suppose you need to do a PET scan on a patient, but the patient is diabetic. Would a PET scan be a good option? Why or why not?

 

References:

 

National Center for Biotechnology Information. "PubChem Compound Summary for CID            11469444, [18F]Fluorodeoxyglucose" PubChem,

            https://pubchem.ncbi.nlm.nih.gov/com...rodeoxyglucose. Accessed 3          September, 2021.

Rudd, J.H.F., et al. “Imaging Atherosclerotic PLAQUE Inflammation with [ 18 f]-Fluorodeoxyglucose Positron Emission Tomography.” Circulation, vol. 105, no. 23, 2002, pp. 2708–2711., doi:10.1161/01.cir.0000020548.60110.76.

Yu, S. “Review of 18F-FDG Synthesis and Quality Control.” Biomedical Imaging and Intervention Journal 2 (2006): n. pag.

Rudroff, Thorsten, et al. “[18F]-Fdg Positron Emission Tomography—an Established Clinical Tool Opening a New Window into Exercise Physiology.” Journal of Applied Physiology, vol. 118, no. 10, 2015, pp. 1181–1190., doi:10.1152/japplphysiol.01070.2014.