Dangers of PET Scans

by

By David W. Brown

Positron emission tomography (PET) scans are diagnostic imaging procedures that utilize radioactive tracers to visualize physiological processes in the body. Although PET scans are used for clinical diagnostics and monitoring disease progression, concerns have arisen regarding their potential to induce genetic mutations leading to cancer. This article explores in detail how PET scans may cause mutations by examining the underlying chemistry, radiation physics, and crude biochemical pathways involved.

Basics of PET Scanning

PET scans utilize radiopharmaceuticals, typically fluorodeoxyglucose (FDG) labeled with radioactive fluorine-18 (18F). FDG resembles glucose, enabling it to be preferentially absorbed by metabolically active cells, such as cancer cells. The radioactive fluorine emits positrons, which quickly collide with electrons, causing annihilation and the subsequent emission of two gamma photons detectable by the PET scanner.

Radiation Chemistry and Mutagenesis

Radiation from PET scans consists primarily of gamma photons, high-energy electromagnetic radiation capable of penetrating tissue deeply and interacting with cellular molecules. The interactions can cause direct or indirect damage:

  • Direct damage occurs when gamma photons directly interact with DNA molecules, breaking chemical bonds, leading to single-strand and double-strand DNA breaks.
  • Indirect damage arises primarily from the interaction of gamma photons with cellular water, forming highly reactive free radicals such as hydroxyl radicals (·OH), superoxide radicals (O₂·⁻), and hydrogen peroxide (H₂O₂).

Formation of Reactive Oxygen Species (ROS)

The major indirect pathway of PET-induced mutations involves the generation of reactive oxygen species (ROS). Gamma photons from PET scans interact with cellular water molecules, creating radiolysis products:

These hydroxyl radicals (OH·) and hydrogen radicals (H·) are highly reactive and unstable, quickly reacting with oxygen to form other ROS:

  • Hydroxyl radicals (OH·)
  • Superoxide radicals (O₂·⁻)
  • Hydrogen peroxide (H₂O₂)

These ROS can diffuse through cells and reach the DNA, causing oxidative damage to nucleotide bases, sugars, and the phosphate backbone.

DNA Damage by Reactive Oxygen Species

ROS cause several types of DNA damage, notably:

  • Base modifications: Hydroxyl radicals can oxidize nucleotide bases, forming modified bases such as 8-hydroxyguanine (8-OHG). This can mispair with adenine during replication, leading to G→T transversions.
  • Single-strand breaks (SSBs): ROS attack the sugar-phosphate backbone, breaking the phosphodiester bonds. SSBs can result in nucleotide deletion or incorrect repair.
  • Double-strand breaks (DSBs): If ROS-induced SSBs occur closely together on opposite DNA strands, they create DSBs. Double-strand breaks are particularly dangerous, as they can lead to chromosomal rearrangements, deletions, and mutations associated with cancer.

DNA Repair Pathways and Mutation Consequences

Cells attempt to repair DNA damage via multiple pathways:

  • Base Excision Repair (BER): repairs base modifications and single-strand breaks but may introduce errors during repair.
  • Non-homologous End Joining (NHEJ): repairs double-strand breaks without requiring a homologous DNA template, prone to introducing mutations such as insertions, deletions, and translocations.
  • Homologous Recombination (HR): a more accurate DSB repair mechanism, requiring a homologous DNA template, usually active during S and G2 phases of the cell cycle.

Errors in these repair mechanisms lead to mutations. Frequent or inefficient repair may accumulate mutations, enhancing cancer risk.

Biological Impact and Cancer Formation

Mutations in critical regulatory genes can initiate carcinogenesis. The relevant genetic targets include:

  • Proto-oncogenes: mutations may activate these genes into oncogenes, causing uncontrolled cellular proliferation.
  • Tumor suppressor genes (e.g., p53, BRCA1, BRCA2): mutations or loss-of-function can disable genomic integrity mechanisms, promoting carcinogenesis.
  • DNA repair genes: mutations impairing these genes amplify genomic instability, significantly elevating cancer risks.

The cumulative effect of these mutations over time significantly raises the probability of neoplastic transformations and cancer initiation.

Dose and Risk Factors

PET scan-associated mutation risks depend on:

  • Radiation dose: Higher doses increase DNA damage likelihood.
  • Frequency of scans: Repeated exposures enhance cumulative radiation dose.
  • Genetic predisposition: Individuals with existing mutations in DNA repair genes are more susceptible to radiation-induced carcinogenesis.
  • Cellular metabolic activity: High metabolic activity tissues (e.g., bone marrow, thyroid) absorb more FDG, thus potentially incurring more extensive radiation-induced DNA damage.

Mitigation Strategies and Clinical Considerations

Strategies to minimize mutation risks from PET scans include:

  • Enhancing antioxidant defenses through dietary means like the P53 Diet to mitigate ROS effects.

Learn more about oxidative stress, hydroxyl radicals, and explore detailed explanations of the Fenton and Haber-Weiss reactions in my books, The P53 Diet & Lifestyle and Taste Versus Cancer.