Positron emission tomography

To study the Pgp function in vivo, several invasive techniques, like Northern blotting and PCR (for detection of mRNA), and immunohistochemistry and Western blotting (for detection of the gene product) are now available. However, due to ethical limitations, tumour biopsies are often hard to obtain. Furthermore, these methods give no insight in the dynamic function of Pgp. PET offers the possibility of probing the physiological function of Pgp in humans in vivo. PET can provide information on drug transport over the BBB via Pgp. For PET studies, a radiopharmaceutical, often a pharmacologically active compound, is labelled with a positron-emitting radionuclide or isotope. After purification and pharmaceutical quality control, the radiopharmaceutical is administered to humans or experimental animals. Because of the short physical

TABLE 1 Substrates of the Pgp drug efflux pump

Cytotoxic agents

HIV1 protease inhibitors

Anti-emetics Opioids

Cardiovascular drugs

Immunosuppressive drugs

Pgp modulators (experimental drugs)

Others

Doxorubicin

Daunorubicin

Paclitaxel

Vincristine

Vinblastine

Etoposide

Actinomycin D

Ritanovir

Saquinavir

Indinavir

Loperamide

Domperidone

Ondansetron

Morphine

Fentanyl

Verapamil

Quinidine

Digoxin

Cyclosporin A

Dexamethasone

Tacrolimus

PSC 833

S 9788

GF 120918

LY 335979

RU 486

Trifluoperazine

Propyl-bis-acridone

Progesterone

Bilirubin

Phenytoin

Ivermectin

Megestrol acetate half-lives of the isotopes (varying from 2min to 110 min), the preparation and purification of a positron-emitting pharmaceutical is a major challenge. After being emitted from the atomic nucleus, the positron travels 2—5 mm and subsequently combines with an electron. The total mass of the particles is then

Positron Emission Tomography Particles

FIG. 2. This schematic represents a positron-emitting (b+) radioisotope. A positron is an anti electron, i.e. a particle with the same mass as an electron but the opposite charge. Such positrons originate during the decay of the nuclei of specific radioisotopes. After travelling a few millimetres through the body, a positron meets an electron. Both particles are then annihilated, producing two g quanta with the same energy (511 keV) but in opposite directions (1808). The g quanta leave the body and are detected by a PET scanner. Detection information is fed into a computer and converted to an image.

FIG. 2. This schematic represents a positron-emitting (b+) radioisotope. A positron is an anti electron, i.e. a particle with the same mass as an electron but the opposite charge. Such positrons originate during the decay of the nuclei of specific radioisotopes. After travelling a few millimetres through the body, a positron meets an electron. Both particles are then annihilated, producing two g quanta with the same energy (511 keV) but in opposite directions (1808). The g quanta leave the body and are detected by a PET scanner. Detection information is fed into a computer and converted to an image.

converted into two photons (511 keV), which are emitted in opposite (1808) directions (annihilation) (see Fig. 2). Due to their high energy, the photons leave the body and are detected simultaneously by two opposite detectors of the PET camera (coincidence detection). The PET data provide quantitative information about the biodistribution of radioactivity in vivo as a function of time.

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