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 on whether respectively gamma or positron emitting radionuclides are used. Imaging methods in nuclear medicine are ideal tools for evaluating the extension of a heart infarction, identifying and localizing tumours and metastases or estimating the degree of development of neurodegenerative diseases. They are now also used 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, i.e., the radionuclides are linked to vectors that bring them specifically to these areas. This simplified description of the process is the basis of vectorised or metabolic radiotherapy, in other words of nuclear medicine for therapy. This efficient therapeutic technology is mainly used to cure cancer patients, but also shows some applications in rheumatology. The use of beam radiations from external sources 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.
The key notion underlying molecular medicine is that diseases have their origin in processes occurring at the molecular and cellular level. Each of us has a unique genetic profile that is reflected through the expression of our genes to the extent that every one of us is visibly and biochemically different. It is the process known as gene expression or how, when and why the genes in our chromosomes are switched on and off, that makes us what we are. Diseases are often associated with changes in the gene expression levels. Our gene expression, and the myriad of different molecular reactions that it triggers in our bodies, now lies at the heart of a paradigm shift that is taking place in the way we diagnose and treat disease, because differences in our genes can dramatically change the way our bodies react to certain drugs. In extreme cases, similar dosages of a drug that are highly effective in one patient can be lethal to another. In other words, it is so personalized that it can be a matter of life or death, and is leading to a whole new field of medicine known as pharmacogenomics, the tailoring of drug therapies to specific genotypes in order to maximize their efficacy and reduce their side effects. It is the biggest change in medicine for the last few thousand years and it is being made possible by developments in molecular medicine.
Pharmacogenomics relies on three different capabilities. First, you can accurately diagnose disease, preferably in its very early stages so that very small doses of highly targeted drugs can be used to cure it before the patient begins to suffer symptoms. Second, you can identify those characteristics of the patient’s genotype that affect the patient’s drug response. And third, you can monitor the patient’s response to therapy in real time, so that you can deliver maximum efficacy with minimum side effects. All three of these capabilities lie within the realm of molecular medicine.
Molecular imaging is one of the pillars of molecular medicine. It involves the development and commercialization of in-vivo bio-marker assays carried out in hospitals using various types of scanning equipment such as Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), Magnetic Resonance (MR), Ultrasound and Optical scanners. The primary objective of this development work is to combine functional imaging with structural imaging so that specific in-vivo molecular processes can be identified and spatially pinpointed, typically through the use of imaging contrast agents that bind to specific biological proteins.
PIED Pet Scan Molecular imaging will therefore fulfill both a diagnostic role and treatment role by allowing doctors to pinpoint disease sites and track the progress of drug therapies. The same contrast agents used to highlight disease sites may even be able to carry drug payloads that can be selectively unleashed precisely where they are needed.
By providing healthcare organizations with an efficient means of identifying and treating disease before patients even begin to suffer symptoms, molecular medicine has the potential to massively reduce the costs associated with late-stage intervention and after-care.
PET (Positron Emission Tomography) is a form of nuclear imaging technology which is based on the particular properties of positron emitter radionuclides (also called ’beta plus rays’). Products labelled 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 SPECT body 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 immediately transform 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 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, 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 labelled 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 cyclotron. FDG 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 tumour 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. However, not all cancers can be easily detected by this technology and it is not appropriate for slowly growing cancers such as prostate cancer. Inflammation and infection processes are also concentrating 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 being installed slowly 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 depends on the capacities of countries to invest in heavy equipment and to solve 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 NMEU and are currently working on common issues that could slow down the access of this extremely helpful technology to patients.
Issues worked on are:
• Regulatory affairs issues
• Safety and compliance issues
• Agreement on quality standards
• Good manufacturing practices
• Reimbursement issues
• New indications