Radioligand administration

PET radiopharmaceuticals are usually administered by intravenous (i.v.) injection. However, in clinical practice, patients with fragile or poorly accessible veins are not uncommon, predisposing to paravenous injections (extravasations) or preventing cannulation. Oral administration of certain PET radiopharmaceuticals, such as [18F]FDG, [18F]fluoride, and [18F]FTHA, may then be an option.

Gaseous radiotracers ([15O]O2, [15O]CO, [15O]CO2, [11C]CO2) may be administered by inhalation. In brain studies the high radioactivity in face mask may cause severe image artifacts when conventional scatter correction methods are used, but appropriate selection of scatter correction method can solve the problem (Magota et al., 2017). Alternatively, gaseous radiotracers can be mixed with blood and administered normally as intravenous bolus.

In mouse studies PET radiopharmaceutical is usually injected into the mouse tail vein. This often leads to extravasation, which may need to be corrected in the data analysis (Vines et al., 2011; Lasnon et al., 2015). Retro-orbital (Yardeni et al., 2011), enteral, or intraperitoneal (Marsteller et al., 2006) administration of radiopharmaceuticals may also be an option in small animal studies (Fueger et al., 2006; Schiffer et al., 2007).

Selective intra-arterial administration has been used in radio- and chemotherapy, and can be used in PET to study these ligands, when labelled with positron emitting isotope; for example the advantage of selective intra-arterial over intravenous administration of BCNU in brain gliomas was demonstrated with 11C-labelled BCNU (Tyler et al., 1986). While intra-arterial administration is not useful in fully quantitative PET studies, it may be very useful during development of new PET radiopharmaceuticals, because it circumvents the problems associated with fast metabolism and clearance in the liver and kidneys (Arnberg et al., 2014).

Intrathecal administration circumvents the blood-brain barrier, which blocks many drugs from entering the central nervous system from the blood. Drug is injected into the spinal canal or subarachnoid space, such as cisterna magna (Glud et al., 2019).

Intranasal administration has been used for drugs targeted for nasal passage, sinuses, or lungs. Intranasal administration has been suggested to offer a way of by-passing blood-brain barrier (BBB) for drug or radioligand delivery to the brain (Lochhead et al., 2015). PET studies with rodents can be used to investigate the delivery of radiolabelled drugs (Ponto et al., 2017). A rodent study with BBB-penetrating radioligands [18F]FDG and [18F]fallypride, has shown that radioligands moved into the olfactory bulb, but not further into the brain; this led to unacceptably high radiation dose to the administration site (Singh et al., 2018).

Administration and sampling sites in circulation

Systemic circulation

After peripheral intravenous injection, radioligand in the blood is transported directly to the heart via the venous network. Blood is first delivered to the right ventricle of the heart, which pumps it through the pulmonary circulation. Small particles (<3 µm) and highly deformable red blood cells can rapidly pass through pulmonary capillaries, while rigid particles with diameter >10 µm are permanently trapped in the lungs. White blood cells, and nanoparticles with size 3-10 µm pass through capillaries slowly, or are initially trapped but can be finally released, travelling to the left ventricle of the heart from where the blood is pumped into the systemic circulation.

Full mixing of injected substance in the entire blood circulation is assumed to be complete in three circulatory transit times, which is ∼3 min in humans, and few seconds in small animals (Chiou, 1989a). Despite of the "full mixing", marked sampling site dependence in venous blood and plasma concentrations are apparent for most compounds (Chiou, 1989a).

Blood accounts for about 6-7% of the body weight, and about half of its volume is red blood cells, and about 1% white blood cells and platelets. Most radioligands are transported in blood bound to plasma proteins and/or inside red blood cells.

See also:


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Updated at: 2020-02-11
Created at: 2014-05-08
Written by: Vesa Oikonen