Metabolic Trapping
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Metabolic trapping refers to a localization mechanism of synthesized radiocompounds in the human body. It can be defined as the
intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
accumulation of a
radioactive tracer A radioactive tracer, radiotracer, or radioactive label is a synthetic derivative of a natural compound in which one or more atoms have been replaced by a radionuclide (a radioactive atom). By virtue of its radioactive decay, it can be used to ...
based on the relative
metabolic activity Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...
of the body's tissues. It is a basic principle of the design of
radiopharmaceuticals Radiopharmaceuticals, or medicinal radiocompounds, are a group of pharmaceutical drugs containing radioactive isotopes. Radiopharmaceuticals can be used as diagnostic and therapeutic agents. Radiopharmaceuticals emit radiation themselves, which ...
as
metabolic Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the ...
probes for functional studies or
tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
location. Metabolic trapping is the mechanism underlying the (
PET A pet, or companion animal, is an animal kept primarily for a person's company or entertainment rather than as a working animal, livestock, or a laboratory animal. Popular pets are often considered to have attractive/ cute appearances, inte ...
) scan, an effective tool for detecting tumors, as there is a greater uptake of the target molecule by tumor tissue than by normal tissue. In order to use it as a diagnostic tool in medicine, scientists have studied the trapping of radioactive molecules within different tissues throughout the body. In 1978, Gallagher et al. studied glucose tagged with
Fluorine-18 Fluorine-18 (18F, also called radiofluorine) is a fluorine radioisotope which is an important source of positrons. It has a mass of 18.0009380(6) u and its half-life is 109.771(20) minutes. It decays by positron emission 96.7% of the time and el ...
(F-18) to see how it metabolized in the tissues of different organs. This group studied how long it took the lungs, liver, kidneys, heart, and brain to metabolize radioactive glucose. They found the molecule distributed uniformly, and then, after two hours, only the heart and the brain had significant levels of radioactivity from the F-18 due to metabolic trapping. This trapping occurred because once the glucose was pulled into the cells, the glucose was
phosphorylated In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writt ...
to cause the concentration of glucose in the cell to appear lower than it is, which then promotes the transport of more glucose. This phosphorylation of the radioactive glucose caused the metabolic trapping in the heart and the brain. The lungs, liver, and kidneys did not experience metabolic trapping, and the radioactive glucose that was not trapped was excreted in the urine. F-18 radiolabeled glucose did not get collected by the kidneys and cycled back into the system, as it would do for normal glucose. This suggests that the
active transport In cellular biology, active transport is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellula ...
er requires the hydroxyl (-OH) group found on the C-2 position of the sugar, where the F-18 atom was placed. Without the active transport, the radiolabeled glucose that was not trapped was then excreted as waste instead of being phosphorylated in the cell. A 2001 study of metabolic trapping used
choline Choline is a cation with the chemical formula . Choline forms various Salt (chemistry), salts, such as choline chloride and choline bitartrate. An essential nutrient for animals, it is a structural component of phospholipids and cell membrane ...
derivatives, which were synthesized using F-18, to label prostate cancer. The experiments were conducted first in mice and then in human patients. Choline (CH) and choline radiolabeled with F-18 (FCH) were both found to primarily migrate to the kidneys and liver in their experiment. This is different from the earlier experiment with glucose due to the difference in mechanism and metabolic need of glucose versus choline in the body. Phosphorylation was again found to be responsible for the trapping of the tracer in the tissues.DeGrado, T. R.; Coleman, R. E.; Wang, S.; Baldwin, S. W.; Orr, M. D.; Robertson, C. N.; Polascik, T. J.; Price, D. T. Synthesis and evaluation of 18F-labeled choline as an oncologic tracer for positron emission tomography: initial findings in prostate cancer. Cancer Res. 2001, 61, 110-117.


See also

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Metabolic imprinting Metabolic imprinting refers to the long-term physiological and metabolic effects that an offspring's prenatal and postnatal environments have on them. Perinatal nutrition has been identified as a significant factor in determining an offspring's lik ...


References

{{Reflist Medicinal radiochemistry Metabolism