Metabolic trapping

Metabolic trapping is a localization mechanism of the synthesized radiocompounds in human body. It can be defined as intracellular accumulation of a drug or radioactive probe depending on metabolic activity of respective tissue.[1] Metabolic trapping is a principle in the design of radiopharmaceuticals as metabolic probes[2] for function or tumor location.[3]

Metabolic trapping is the mechanism through which we analyze the PET Scan (Positron Emission Tomography)[4]. Metabolic trapping is an effective tool for detecting tumors because there is a greater uptake of target molecules by tumor cells than there is for normal tissue, such as that in our organs.

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 (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 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 transporter 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.[5]

Another, more recent study which discussed metabolic trapping was performed by DeGrado et al in 2001. This group used choline 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 experiment above due to the difference in mechanism and metabolic need of glucose versus choline in the body. However, the process of phosphorylation is still responsible for the trapping of the molecules in the tissues.[6]

See also

References

  1. ↑ J.S. Fowler et al. Methods 27 (2002) 263–27
  2. ↑ probe in biochemistry is: Any group of atoms or molecules radioactively labeled in order to study a given molecule or other structure
  3. ↑ . Gallagher, Brian M and et al. Metabolic Trapping as a Principle of Radiopharmaceutical Design: Some Factors Responsible for the Biodistribution of [18F] 2-Deoxy-2-Fluoro-D-Glucose The Journal of Nuclear Medicine 19:1154-1161,1978
  4. ↑ (Miele, E.; Spinelli, G. P.; Tomao, F.; Zullo, A.; De Marinis, F.; Pasciuti, G.; Rossi, L.; Zoratto, F.; Tomao, S. Positron Emission Tomography (PET) radiotracers in oncology–utility of 18F-Fluoro-deoxy-glucose (FDG)-PET in the management of patients with non-small-cell lung cancer (NSCLC). Journal of Experimental & Clinical Cancer Research 2008, 27, 52.)
  5. ↑ . Gallagher, Brian M and et al. Metabolic Trapping as a Principle of Radiopharmaceutical Design: Some Factors Responsible for the Biodistribution of [18F] 2-Deoxy-2-Fluoro-D-Glucose The Journal of Nuclear Medicine 19:1154-1161,1978
  6. ↑ 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.
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