Question

The ability to diagnose tumors using \(\left[{ }^{18} \mathrm{F}\right]\) -fluorodeoxyglucose (FDG) is based on the phenomenon that most types of cancer cells exhibit higher levels of a. glycolysis. b. pyruvate breakdown. c. citric acid metabolism. d. oxidative phosphorylation. e. all of the above.

Short answer

The answer is (a) glycolysis. Cancer cells exhibit higher levels of glycolysis, which can be detected using \(\left[{ }^{18} \mathrm{F}\right]\)-fluorodeoxyglucose (FDG).

Step-by-step solution

Understanding the metabolic processes

Firstly, understand each of the metabolic processes mentioned. Glycolysis is the metabolic pathway that converts glucose into pyruvate. Pyruvate breakdown results in Acetyl CoA, which enters the citric acid cycle, also known as Krebs cycle or TCA cycle. Oxidative phosphorylation, meanwhile, is the metabolic pathway that uses energy released by the oxidation of nutrients to produce ATP. All these processes are part of the cell metabolism cycle.

Identify the metabolic pathway of cancer cells

Research shows that most cancer cells exhibit higher levels of glycolysis, even in the presence of oxygen, a phenomenon known as the Warburg effect. This is a type of anaerobic respiration within cells. Despite the inefficiency in terms of ATP generation compared to oxidative phosphorylation, this path allows cancer cells to accumulate biomass and divide more rapidly, adding to the aggressive growth of cancers.

Identifying the role of FDG

Lastly, understand the role of \(\left[{ }^{18} \mathrm{F}\right]\)-fluorodeoxyglucose (FDG) in detecting tumors. FDG is a glucose analogue; it competes with glucose for transport into the cell and for phosphorylation by hexokinase. Once phosphorylated, it cannot continue further in glycolysis, so it gets trapped inside the cell. Because cancer cells exhibit higher rates of glycolysis, they uptake more FDG. The \(\left[{ }^{18} \mathrm{F}\right]\) in FDG can be detected with Positron emission tomography (PET) scan, creating a visualization of areas with high FDG uptake, like tumors.

Key concepts

Glycolysis

Glycolysis is the first step in the pathway that helps cells extract energy from glucose. It occurs in the cytoplasm and transforms one molecule of glucose into two molecules of pyruvate. This process generates a small amount of energy, in the form of two ATP molecules, and two NADH molecules. Glycolysis is unique because it doesn't require oxygen, making it an anaerobic process. This means it can function regardless of oxygen levels.

In cancer cells, glycolysis is notably heightened, even when oxygen is present. This phenomenon, called the Warburg effect, allows cancer cells to support rapid growth and survival. This increased glycolytic rate leads to a higher uptake of glucose by cancer cells.

FDG-PET Scan

FDG-PET scans utilize a modified form of glucose to image the body. FDG stands for \(()=>^{18}F\)-fluorodeoxyglucose, a glucose molecule marked with a radioactive tracer. This tracer behaves similarly to glucose, allowing the scan to track its movement through the body. When a patient is given FDG, it accumulates in areas of high glucose uptake, such as tumors.

The PET scan detects these areas with radioactivity, highlighting spots where cancer cells are active. This technique is incredibly useful in diagnosing and monitoring cancers since it exploits the cancer cells' reliance on glucose through glycolysis.

Cancer Cell Metabolism

Cancer cell metabolism is distinct due to its reliance on glycolysis over other energy generation pathways. Even in the presence of abundant oxygen, cancer cells often prefer glycolysis, which is a less efficient energy producer than oxidative phosphorylation. Known as the Warburg effect, this reliance may be puzzling.

However, glycolysis supports the fast cell growth associated with cancer by providing the cell with not only some ATP but also crucial biomolecules needed for proliferation. Cancer cells use the intermediates of glycolysis to synthesize DNA, proteins, and lipids, which are crucial for cell replication and tumor growth.

Glucose Uptake

Glucose uptake involves the movement of glucose across the cell membrane, facilitated by glucose transporters. Cells require glucose as a major energy source. In cancer cells, this uptake is significantly elevated due to their high demand for glucose to fuel their increased metabolic activities.

Fluorodeoxyglucose (FDG), a radiolabeled glucose derivative, takes advantage of cancer cells' heightened glucose uptake. Upon entering cancer cells, FDG competes with natural glucose, allowing it to become trapped inside and visible under imaging scans, such as the PET scan used in cancer diagnostics.

Anaerobic Respiration

Anaerobic respiration refers to the production of energy from glucose without the need for oxygen. Glycolysis, a key part of anaerobic respiration, creates pyruvate which, in the absence of oxygen, is converted to lactate instead of entering the citric acid cycle.

While less efficient in terms of ATP yield compared to aerobic respiration, anaerobic respiration supports quick energy release and rapid cell division. This is advantageous for cancer cells, which exploit this process to sustain uncontrolled growth and division, characteristic of tumors. The adaptation to anaerobic pathways in the presence of oxygen showcases the versatility and aggressiveness of cancer cell metabolism.