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Seeing Beneath the Surface: The Power and Limitations of PET-CT Imaging

April 23, 2025

When doctors want to see deeper into your body, PET-CT is a popular choice. It is a super powerful imaging tool that is widely used in diagnosis, staging, and monitoring of various diseases, particularly in oncology, cardiology, and neurology. It’s especially useful in detecting cancer, guiding treatment plans, and understanding conditions affecting the heart or brain. But how does it actually work — and why does it matter so much? Let’s figure it out.

What is PET-CT exactly? The answer is quite straightforward. It is just PET plus CT! This means before we get into PET-CT, we have to learn about both PET and CT.

Taking advantage of radioisotope signals, PET is an imaging method that enables the measurement of the change in metabolic activities and other physiological activities in vivo (Fowler & Volkow, 2022). All the radioisotopes are positron emitters that will emit positrons to keep them stable. Gamma rays will be produced and detected by sensors, which will be mapped. After millions of records, a clear map that provides information about the quantity and location of the positrons in the body will be produced (Basu et al., 2011).

When interpreting the PET scanning image, the hot spots and the cold spots are what we need to focus on. Hot spots are the regions with bright colors (white, yellow, orange, and red). In these regions, the uptake rate of the radiotracer is higher, which indicates a higher rate of metabolic activity. Therefore, these regions will represent cancer, inflammation, or active regions of our body. Cold spots, on the contrary, represent dead tissue and reduced function that lower metabolism in that region (TerPogossian et al., 1980).

Computed tomography (CT) is what we are more familiar with. It is a frequently used and widely available non-invasive imaging modality and has been applied in measuring the size of body tissues like bones, muscles, and brains. X-rays will be emitted from different directions, pass through the body, and be received by the detector, forming images of projections of the body in different directions. Through computer calculation based on the X-ray attenuation characteristics of the tissues within the voxel, sizes of targeted tissues will be measured (Mazonakis & Damilakis, 2016).

With the basic knowledge of both PET and CT, it is easy to understand that PET-CT is just a combination of the two technologies. It can trace both the change in metabolism of the tissue and the size of it. On the other hand, the combination of these two technologies is quite revolutionary. One of the biggest limitations of a PET scan is its lack of spatial resolution and a clear anatomical reference frame. This defect hinders PET from accurately presenting the anatomic structure of lesion tissues, which negatively affects diagnosing diseases such as cancers and Alzheimer’s disease. Fortunately, CT addresses this problem. When combined, PET shows functional activity and CT shows structure, helping distinguish between normal and pathological signals. This fusion is especially important in cancer diagnosis, where identifying the exact location and stage of a tumor is critical for accurate treatment planning (Basu et al., 2011). With different kinds of radiotracers, PET-CT can be used in different aspects of imaging, including glucose metabolism, tumor proliferation, myocardial perfusion imaging, skeletal imaging, and brain imaging (Anand et al., 2009).

With a lot of advantages, PET-CT is pervasively used around the world. Besides improving the accuracy of diagnosis, PET-CT also contributes to the early detection of certain cancers and the early detection of cancer recurrence, impacting patient management by assisting in defining potential candidates for curative surgery, planning the appropriate surgical or radiotherapy approach, and referring patients with unresectable disease to other therapeutic options (Israel & Kuten, 2007).

It is clear that PET-CT is a life-saving tool for humans. However, there are still limitations we need to overcome. One of the major limitations of PET-CT as a cancer screening tool is its radiation exposure, which poses a potential health risk, especially when used routinely in healthy people. A standard PET-CT scan involves both a radioactive tracer and a CT scan. It is a combined radiation dose that can be significantly higher than most diagnostic imaging tests. This raises concerns about the long-term effects of repeated exposure, particularly in asymptomatic populations. Additionally, high cost and questionable cost-effectiveness further limit its practicality. PET-CT scans are expensive. When they detect abnormalities, they often lead to further testing and interventions, but many of them are unnecessary due to false positives or clinically insignificant findings. Moreover, PET-CT has limited sensitivity for certain cancers, especially those that are slow-growing or have low glucose metabolism, such as early-stage prostate cancer or some lung adenocarcinomas. These cancers may not show up clearly on PET scans, which could give patients a false sense of security and delay diagnosis. Overall, while PET-CT has diagnostic value in high-risk or symptomatic individuals, its limitations make it a controversial and potentially problematic tool for routine cancer screening in the general population (Schöder & Gönen, 2007).

Despite its remarkable capabilities, PET-CT is not without challenges. While it has revolutionized the way we diagnose and monitor diseases, especially cancer, it is not yet ideal for general screening. The combined radiation dose, high cost, and limited sensitivity for certain low-activity cancers mean that routine use in healthy individuals may do more harm than good. False positives can lead to anxiety, unnecessary procedures, and added burden on healthcare systems. Still, in the hands of experienced clinicians and when used appropriately—particularly in high-risk or symptomatic patients—PET-CT remains an invaluable tool that can save lives by guiding targeted treatment decisions. As research continues and technology advances, there’s hope that PET-CT will become safer, more affordable, and even more precise. Until then, its greatest value lies in thoughtful, case-by-case application rather than widespread use for screening the general population. After all, smarter imaging leads to smarter care.

 

 

References

Featured image from Metastatic Trail Talk https://metastatictrialtalk.org/from-the-experts/pet-ct-scans/

Anand, S., Singh, H., & Dash, A. (2009). Clinical Applications of PET and PET-CT. Medical Journal Armed Forces India, 65(4), 353–358. https://doi.org/10.1016/s0377-1237(09)80099-3

Basu, S., Kwee, T. C., Surti, S., Akin, E. A., Yoo, D., & Alavi, A. (2011). Fundamentals of PET and PET/CT imaging. Annals of the New York Academy of Sciences, 1228(1), 1–18. https://doi.org/10.1111/j.1749-6632.2011.06077.x

Fowler, J. S., & Volkow, N. D. (2022). Molecular Imaging: Positron Emission Tomography. Neuroscience in the 21st Century, 3297–3321. https://doi.org/10.1007/978-3-030-88832-9_149

Israel, O., & Kuten, A. (2007). Early Detection of Cancer Recurrence: 18F-FDG PET/CT Can Make a Difference in Diagnosis and Patient Care. Journal of Nuclear Medicine, 48(1 suppl), 28S35S. https://jnm.snmjournals.org/content/48/1_suppl/28S.short

Mazonakis, M., & Damilakis, J. (2016). Computed tomography: What and how does it measure? European Journal of Radiology, 85(8), 1499–1504. https://doi.org/10.1016/j.ejrad.2016.03.002

Schöder, H., & Gönen, M. (2007). Screening for Cancer with PET and PET/CT: Potential and Limitations. Journal of Nuclear Medicine, 48(1 suppl), 4S18S. https://jnm.snmjournals.org/content/48/1_suppl/4S.short

TerPogossian, M. M., Raichle, M. E., & Sobel, B. E. (1980). PositronEmission Tomography. Scientific American, 243(4), 170–181. JSTOR. https://doi.org/10.2307/24966439

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  Timothy Durham was convicted of rape when a test showed his DNA genotype matched the DNA recovered from the crime scene. Eye witnesses testified that Durham was in a different state at the time of the incident, but he wasn’t exonerated from his 3000 year sentence until follow up DNA analysis showed that the preliminary forensic analysis used in the trial was misinterpreted (Thomas et al.). DNA testing serves an invaluable part in our criminal justice system, but it comes with complications and bias that can lead to wrongful convictions and misinformed juries.  

Background:

Forensic genetics aims to identify the origin of a biological sample. It can be traced back to Karl Landsteiner who discovered human ABO blood groups. With blood groups, suspects could be eliminated based on their blood type. For example, if a suspect had type A blood and there was type B blood left at the scene by the perpetrator, the investigators could rule out the suspect. Unfortunately, the reverse didn’t work. If the suspect and perpetrator both had the same blood type, it can’t be concluded that the suspect was guilty. Blood identifiers evolved into 8 distinct categories which improved the ability to eliminate suspects, but could only conclude that (if the system matched) it might be the perpetrator or this person might be related to the perpetrator (Jobling and Gill). The field evolved in the 1980s with the discovery of Minisatellites, lines of repetitive DNA that don’t encode proteins. Minisatellite patterns in DNA create what we know today as the DNA fingerprint, and it has a much higher accuracy rate than previous methods (Augustyn et al.). Around the same time, a breakthrough for victims of sexual assault was discovered. In the case of assault, bodily fluids of both the victim and the assaulter can get mixed. A process called differential lysis was created which could selectively increase the concentration of sperm in a fluid sample thereby allowing for accurate DNA testing (Jobling and Gill). Forensics evolved to use single-locus probe testing after several years because of its ease of interpretation. It looked at specific minisatellites that had high variability between subjects. This was the first DNA-based method to be used in a criminal investigation. Two murder homicides from several years apart were connected using DNA evidence. The evidence was then used to exonerate an innocent man, and the guilty party was found when he tried to evade mandatory DNA testing for all men in the small town. His guilt was then reinforced when the DNA profiles matched, and he gave a confession (Jobling and Gill). Finding DNA at a crime scene doesn’t guarantee that you’ll find a murderer. There are issues with non-pure samples and limited samples that make DNA work difficult, and accreditation of facilities and new techniques and take time (Jobling and Gill).  

Subjectivity of DNA Interpretation:

In a 2009 publication, the National Academy of Science discusses the possibility for subjective influence in lab based forensics. The interpretation bias happens in complex cases where, for example, there could be a mixture of DNA. A study published in 2011 looked specifically at this issue. A gang rape happened in Georgia, and the mixture in DNA from the case was used to prosecute one suspect after another suspect took a plea bargain to testify against him. With DNA mixtures, there are three possible conclusions: suspect excluded, suspect cannot be excluded, and inconclusive. If the suspect is excluded, it means that there’s little to no possibility that his DNA is part of the sample. If the suspect cannot be excluded, it means that there’s a possibility that his DNA is part of the sample. In the trial, the DNA examiners who knew the context of the case concluded that the suspect being prosecuted could not be excluded. The 2011 study gave the DNA evidence from this case and the DNA profiles of the suspects to 17 forensic examiners. These examiners had no context of the case, and they all worked independently. Of the 17, only 1 came to the same conclusion (suspect cannot be excluded) as the examiners who knew the context of the case. Twelve of the 17 concluded that the suspect who was prosecuted and convicted had no relation to the DNA found in the sample. Not only does this show that subjectivity occurs due to the context of the case, but the 17 examiners came up with different findings based on their past experiences meaning that not all DNA analysis is objective. Some organizations like the Scientific Working Group on DNA Analysis Methods say that quantitative statistical evidence should be presented with every categorical conclusion, but the US doesn’t require this (Dror and Hampikian).

False Positives:

There are two categories that cause wrongful identification in a DNA report: coincidental matches and false positives. Coincidental matches are DNA matches between two unrelated people. The probability of these matches is about 1 to 500,000 for white individuals and about 1 to 350,000 for black individuals. This small probability of coincidental matches makes people feel confident in DNA evidence. False positives, on the other hand, are matches between DNA and test DNA that result from issues in the forensics lab. There have been multiple cases of forensics labs accidentally switching victim and suspected rapist DNA which lead to convictions that were later overturned when the lab realized the error. There are also cases of misreading or misunderstanding a sample. In a case from 1993, a man was convicted of rape because someone interpreted a mixed sample of victim and perpetrator DNA as an individual sample. The conviction was again overturned. To prevent false convictions, retesting DNA is allowed, but it’s not an efficient solution. Many people are pushing for statistical information on the probability of false positives, so that the jurors can make accurate judgements based on DNA evidence (Thomas et al.).  

Conclusion:

DNA analysis is a useful tool for the criminal justice system, but subjectivity can be an issue in forensic testing. To combat wrongful convictions, there are organizations like The Innocence Project who use DNA testing to free the innocent, but reformed forensic testing standards should be put in place to prevent subjectivity and to ensure juries are correctly informed during trials. https://www.innocenceproject.org/    

Citation:

Augustyn , Adam, et al. “DNA Finerprinting.” Encyclopedia Britannica , 26 Apr. 2018, www.britannica.com/science/DNA-fingerprinting#ref153186. Dror, Itiel E., and Greg Hampikian. “Subjectivity and Bias in Forensic DNA Mixture Interpretation.” Science & Justice, vol. 51, no. 4, 2011, pp. 204–208., doi:10.1016/j.scijus.2011.08.004. Jobling, Mark A., and Peter Gill. “Encoded Evidence: DNA in Forensic Analysis.” Nature Reviews: Genetics, vol. 5, no. 10, Oct. 2004, pp. 739–751., doi:10.1038/nrg1455. Thompson, William C, et al. “How the Probability of a False Positive Affects the Value of DNA Evidence.” Journal of Forensic Sciences, vol. 48, no. 1, Jan. 2003, pp. 1–8., doi:10.1520/jfs2001171.