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Physiologic
Principles Used in PET: FDG Uptake Mechanism in
Oncology.
Fluoro-2-deoxyglucose
(FDG) is one of the most commonly used radionuclides
in clinical PET. Two-deoxyglucose is a glucose analogue
that is as avidly accrued by tumor cells as is glucose.
Labeling this compound with Fluorine-18 allows one
to measure or image this glucose accumulation as
a function of the positron emitter (to measure positron
emission as a reflection of glucose accumulation).
Normally, once glucose enters into a cell (via a
transporter enzyme) it is phosphorylated by an enzyme
called hexokinase and then enters directly into
either the glycolytic or glycogenic pathway. Once
the compound FDG is intracellular, it undergoes
the phosphorylation step but is subsequently unable
to continue into the usual glucose metabolic pathways
(due to the presence of flourine) and is essentially
trapped in the cell as FDG-phosphate.
Different human tissues will have different amounts
of hexokinase and glucose-6-phosphatase present,
resulting in different patterns of intracellular
FDG accumulation. For example the ratio of the concentration
of hexokinase to glucose-6-phosphatase is higher
in the brain and heart than in other tissues, so
that the FDG accumulation in these tissues is predictably
higher than in others.
Many studies have shown, over the past 70 years
have shown that tumors tend to have an increased
rate of glucose utilization with respect to normal
tissue. Several reasons may account for this finding
including:
- Increased
transport of glucose into tumor cells, in part
due to an increase in the concentration of the
carrier protein.
- An
increase in the concentration and affinity of
the enzyme hexokinase due to the extra energy
demands of an actively and abnormally dividing
cell population.
- Increase
in glycolytic enzymes such as pyruvate kinase,
phospho-fructokinase, and pyruvate dehydrogenase.
The
dephosphorylation rate in tumor cells may be slower
than in normal cells. It then follows that the accumulation
of FDG-6-phosphate can be used to assess a tumor's
glycolytic rate, which in turn is proportional to
a tumor's proliferation rate and reflective of a tumor's
aggressiveness and rate of growth.
Although various isotopes have been used in clinical
and research PET (including O-15, C-11methionine,
F-fluorodopa) two of the most commonly used compounds
are N-14-ammonia and F-18-FDG. F-18-FDG is currently
the main clinical isotope in oncology, neurology
and cardiology.
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