What is Nuclear Medicine?

Nuclear medicine is a specialized field of medicine covering all aspects of the use of radioactive substances that are either injected in or ingested by humans with the aim to diagnose or treat a disease. Imaging of tissues or organs can be  obtained through the particular properties of radioactivity that produces highly energetic light (such as gamma rays). Radioactive substances concentrate in specific cells and tissues as a consequence of the grafting of radioactive atoms (radionuclides) to drugs that have the property to recognize and therefore stay in these specific cells. In general cells undertaking transformation, growing or dying, such as tumor cells or ischemic tissues in heart, can easily be differentiated from normal neighboring cells, as their biology is altered. Special cameras able to detect the radiations that are emitted from these zones where the drug is concentrated provide nice images of this area. The physician can therefore easily evaluate the extension of the affected area, recognize the disease and provide a diagnostic.
 
 

 
As very small, infinitesimal quantities of radionuclides are used, there are no side effects due to the radio-activity, which also has a very short life. Depending on the type of radiation, detection equipment must be adapted. Thus, SPECT (Single Photon Emission Computed Tomography) or PET (Positron Emission Tomography) will be used depending if respectively gamma or positron emitting radionuclides will be used. Imaging methods in nuclear medicine are ideal tools for evaluating the extension of a heart infarction, identifying and localizing tumors and metastases or estimating the degree of development of neurodegenerative diseases. They are now also use to follow the efficacy of a therapy. Due to its sensitivity, nuclear medicine detects very faint sources of radioactivity and is therefore ideal for early detection of very small lesions. Another form of radioactivity is expressed by the emission of particles instead of gamma rays. These alpha or beta minus radiations destroy cells by ionization and can therefore be used to kill unwanted cells, if based on the same principle as imaging agents, the radionuclides are linked to vectors that bring them specifically to these areas. This simplified description of the process is the basis of vectorized or metabolic radiotherapy, in other words of nuclear medicine for therapy. This efficient therapeutic technology is mainly used to cure cancer patients, but shows also some applications in rheumatology. The used of beam radiations from external source is called external radiotherapy, and is not part of nuclear medicine, while the use of X-rays, another form of energetic radiation, belongs to the domain of the radiologist.
 
 

What is PET?

PET is a form of nuclear imaging technology whose acronym stands for Positron Emission Tomography. It is based on the particular properties of positron emitter radionuclides (also called 'beta plus rays'). Products labeled with these radionuclides are injected into patients and the biological properties of the molecule on which they are bound result in a concentration in specific cells that recognize these molecules. In fact, this principle is not different from the more common SPECT (Single Photon Emission Computed Tomography) imaging technology, but the special use of beta emitters requires the detection of the radiation to be done with special equipment.
 
 
 

 

 

A positron is in fact an anti-electron, or more accurately, a positively charged electron, that cannot survive in the natural environment. This particle of anti-matter is ejected by the radioactive atom when it decays. Its function is to look for a normal electron and as soon as it collides with it, the two particles transform immediately into pure energy (the annihilation effect) in the form of two photons (light) that are moving in the exact opposite direction of one another. If one installs two detectors on both sides, it becomes easy to detect, with exceptional precision, at least the direction from where this light beam is emitted from. With detectors installed in a crown around the source of radiation, it becomes possible to see the origin of the beta plus the radiation in the same plane. By moving this crown of detectors along the body of the patient, one can collect enough information to get a three dimensional mapping of the source of the radiation. In the past couple of years, the PET cameras have been combined with three dimensional X-ray imaging cameras and equipment suppliers are now able to offer combined PET-CT machines. A very recent technological development has allowed new, highly precise measuring equipment to be placed on the market. This new equipment can measure the origins of the two photons with a high degree of accuracy. In effect, it measures the difference in the time of flight of the photons that are hitting the opposite detectors at the speed of light and therefore enhances the precision of the positioning.

 
 

Today, almost all PET imaging modalities are based on a unique drug called FDG (Fludeoxyglucose). This sugar molecule is labeled with Fluorine 18, the most common beta emitter isotope that has a half life of only two hours. The advantage of this very short half-life means that the radioactivity in the patient completely disappears by the end of the day. However, it is also the most constraining property influencing the manufacturing and application of FDG. Fluorine 18 is produced daily with a piece of special heavy equipment called a cyclotronFDG concentrates itself in all tissues that are consuming sugar. Primarily, this will be the brain and the heart, which are organs that permanently need sugar. But this has a limited interest. It appears that tumor cells consume glucose up to 30 times faster than the surrounding normal cells and therefore FDG becomes an ideal imaging agent for cancer detection, staging and therapy follow-up. Not all cancers can be easily detected by this technology, however and it is not appropriate for slowly growing cancers such as prostate cancer. On the other hand, inflammation and infection processes are also concentrated FDG and can result in false positive interpretation, if not validated by an expert nuclear physician.  On this basis, new imaging tools are being developed to answer the questions that cannot be solved by FDG, but still use PET technology. These new molecules under development will target other cancer pathologies, but will also be useful in predicting the evolution of neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. These new drugs will be based on new vectors and biological mechanisms, as well as beta plus emitting radionuclides different from Fluorine 18 such as Iodine 124 or Gallium 67.

There are presently two limitations in the development of the PET technology:
  • The hospitals must be equipped with these special PET devices; cameras are only slowly being installed in European countries.
  • The short half life of the fluorine obliges manufacturers to install cyclotrons and FDG manufacturing centers at less than three hours driving distance from hospitals.

Therefore, an area is equipped with cameras only if there is some investment in a cyclotron, while a cyclotron will be implemented only if there is a guarantee that governments will invest in a minimum number of cameras. Hence, the development of this technology is therefore dependent on the capacities of countries to invest in heavy equipment and to find issues to reimburse this modality to patients.

The cyclotron producers, the pharmaceutical grade FDG suppliers and the PET camera manufacturers working in Europe are all present within the AIPES and are currently working on common issues that could slow down the access of this extremely helpful technology to patients. Some of the issues that the working group that was specifically created to handle the issues related to PET and its technology is dealing regularly with are:

  • regulatory affairs issues
  • safety and compliance issues
  • agreement on quality standards
  • good manufacturing practices
  • reimbursement issues
  • new indications

This group works in close cooperation with the Regulatory Affairs working group as well as with the New Technologies working group. All AIPES members involved in the PET business have at least one representative in this working group.