Produced Radiopharmaceuticals

The most frequently used radiopharmaceuticals in oncology is F-18-labeled 2-fluoro-2-deoxyglucose, 18F-FDG.

Normally, common glucose is mainly transported into the cells through the membrane glucose receptors (Glucose Transporters-GLUT) by facilitated diffusion. When glucose enters the cells, it is phosphorylated by the enzyme hexokinase and, in normal circumstances, it continues on its metabolic pathway of glycolysis for the production of energy.
In the case of 18F-FDG, transport into the cell through the GLUT receptors and phosphorylation through hexokinase occur in the same way as with common glucose. However, the lack of oxygen in position 2 in the 18F-FDG molecule impedes further glycolysis and, as a result, the phosphorylated molecule remains undivided and trapped within the cell. Thus, a high concentration in 18F-FDG reflects an increased glucose metabolism, as it happens, for instance, in cancer cells.

The high accumulation of 18F-FDG in cancer cells is due to:

• The increased expression and reactivity of glucose transporters-GLUT.
• The increased production and reactivity of hexokinase.
• The lack or the low levels of phosphatase.

Other radiopharmaceutical which has been licensed by the Greek National Organization for Medicines (EOF) and is being used in Greece is 18F-labelled choline (18F-CHOLINE). 18F-CHOLINE is incorporated in the cell membrane through its transformation into 18F-phosphorylocholine, which is trapped within the cell and is followed by the synthesis of 18F-phosphatidylcholine (lecithin), which is the main component of the cell membrane. As cancer cells multiply very rapidly, the biosynthesis of the cell membranes is also very rapid and is related to an increased uptake of choline and an upregulation of the choline enzyme, kinase. The uptake of 18F-CHOLINE in terms of volume is proportional to the rate of multiplication of cancer cells. 18F-CHOLINE has been used with various indications, but today its main application is the imaging of prostate cancer.

The development of neoplasms is based on a continuously increasing population of cancer cells which do not respond to the control mechanisms of cell division. Radiolabelled compounds, DNA precursors, nucleotides, which are incorporated in the DNA during the S-phase of the cell cycle, can be used as radiopharmaceuticals in PET for the measurement of cell multiplication. 18F-FLT is a thymidine analogue, wherein the hydroxyl group in 3-position has been replaced by fluorine. After its uptake by the cells is completed, it is phosphorylated by thymidine kinase 1, but the next step in the DNA synthesis is impeded by the replacement of ΟΗ- with F- and, thus, 18F-FLT is trapped within the cell. Many studies have been realized for the use of 18F-FLT in different types of cancers, such as lung cancer, breast cancer, gastrointestinal cancer, head and neck cancer, primary brain tumours, melanoma and non-Hodgkin lymphoma, as well as in the characterization of solitary pulmonary nodules. However, even if 18F-FLT was introduced as a multiplication marker for various types of neoplasms, it is also a very promising method in cases of primary brain tumours, as it can distinguish between low-grade and high-grade gliomas and it provides information for the extent and activity of these tumours. Furthermore, the most interesting field of research in the use of 18F-FLT today is the examination of the response of various tumours to treatment.

18F-ΝaF is used in bone imaging. Its uptake is the result of an exchange of ions between the hydroxyl groups in the hydroxyapatite of the bones and the formation of fluoroapatite and it is, therefore, directly related to bone metabolism. Compared to bone scintigraphy, PET/CT with the use of 18F-ΝaF seems to offer higher accuracy in the detection of bone metastases (osteoblastic and osteolytic).