New research reveals important limitations of FDG-PET scans of atherosclerosis

Doctors often use different types of scans for establishing diagnoses in patients and to monitor effects of therapy. Scans also play an important role in medical research, e.g. to monitor the effects of new treatments. A research group from Aarhus University and Aarhus University Hospital has developed a new method with potential significance in the development and evaluation of future therapies, e.g. against arteriosclerosis. The method reveals that the world's leading type of positron emission tomography (PET) scan of atherosclerosis using FDG (Fluoro-Deoxy-Glucose) has important limitations. The method is described in a study published in the scientific journal, Journal of the American College of Cardiology (JACC).

The research group has developed a method for precise quantification of PET scans and validated the method with the help of advanced computer simulations. The utility of medical scans is often limited by the low resolution of the images, which makes it difficult to obtain quantitative measures of small structures. The new method makes it possible to quantify the radioactive tracer used for a PET scan, even in very small structures such as an artery wall.

One of the researchers, Rozh Al-Mashhadi, who is a medical doctor at the Department of Radiology, Aarhus University Hospital, describes the research: "With the new technique, we can quantify how the PET tracer, FDG, is absorbed in the wall of arteries. We find that FDG-PET is not a specific measure of disease activity in atherosclerosis. Importantly, the quantification approach that we have developed can be used to investigate other promising PET tracers that may guide the evaluation of new treatments against atherosclerosis.”

"The quantification approach is not restricted to arteriosclerosis research, but has potential utility in other areas of nuclear medicine and may contribute to better our understanding of various other disease processes." emphasises Rozh Al-Mashhadi.

Candidate drugs rejected on the basis of inaccurate tests

Rozh Al-Mashhadi, who is lead author of the scientific paper published in JACC, explains that the main focus of the new study is the biological element: "The new and more precise quantification technique has revealed serious limitations in the test scan that has been often used for evaluation of potential anti-atherogenic drugs. Specifically, FDG-PET has been used to examine the effect of medications against arteriosclerosis, and many promising drugs have been rejected as ‘ineffective'. However, we show that FDG-PET cannot be used as an exact measurement of the effects of these treatments," explains Rozh Al-Mashhadi about the research which has been conducted in pigs. Porcine disease models are particularly suitable for atherosclerosis research because pigs have a cardiovascular system that is similar to that of humans.

Millions of dollars at stake

The study is interesting for both the research community and the pharmaceutical industry. The development of new drugs is costly, and it is therefore essential that new treatments are not rejected on the basis of inaccurate scans.

"There is a lot at stake in this research field. Developing and testing new drugs runs into millions of dollars and the entire investment is lost if the medicine is found ineffective. It is therefore important that the effect of new drugs is tested using accurate methods. Importantly, we must also consider the cost for the participants in drug trials who may undergo unnecessary scans." says Rozh Al-Mashhadi.

The scientific importance the new study from Aarhus University is emphasized by its publication in JACC accompanied by an editorial written by two highly prominent figures in the field, Peter Libby and Marcelo De Carli, both professors at Harvard University.

According to Rozh Al-Mashhadi, this is a seal of approval but also an obligation.

"We have been very meticulous in validating our methodology, especially because we raise concerns regarding a scan technique that is considered valid by many in the atherosclerosis research community. While the study may not have direct effect on patients suffering from atherosclerosis, it may contribute to enhance our methods for testing new treatments against this highly prevalent vascular disease.”

Facts

• A PET scan is conducted following injection of a radioactive tracer, e.g. FDG which is a modified sugar molecule.
• The lifetime risk of developing atherosclerosis-related cardiovascular disease is approximately 40% for females and 50% for males.
• Cardiovascular disease is the leading cause of mortality globally.

About the study

• Type of study: Basic experimental research
• Contributing researchers: Professor Jacob F. Bentzon, Department of Clinical Medicine, Aarhus University; Hospital Physicist Lars P. Tolbod, Department of Nuclear Medicine & PET Centre, Aarhus University Hospital; and Professor Jørgen Frøkiær, Department of Clinical Medicine, Aarhus University.
• Funding: The Independent Research Fund Denmark, The Danish Heart Foundation, The Lundbeck Foundation, Aarhus University Research Foundation (AU IDEAS).
• Potential conflicts of interest: none.
• Link to the scientific article: http://www.onlinejacc.org/content/74/9/1220.full

Contact:

Rozh H. Al-Mashhadi, MD, PhD
Department of Clinical Medicine, Aarhus University and Department of Radiology, Aarhus University Hospital
Email: rham@clin.au.dk