DOTA (1,4,7,10-tetraazacyclododecane-N,N’,N”,N”’-tetraacetic acid) forms chelates with metals, which has been widely applied in production of radioligands for SPECT, MRI, and PET. DTPA (diethylene triamine pentaacetic acid) has similar properties. Usually, DOTA and DTPA are used to link metal ion to a peptide or other large organic molecule with specificity to a certain receptor or metabolic process.
Gadolinium ion (Gd3+) chelates (Gd-DOTA and Gd-DTPA) have been used as a contrast agent in MRI, for example to measure myocardial perfusion (Larsson et al., 2001; Pärkkä et al., 2006), viability (Pereira et al., 2001), extracellular volume (Banypersad et al., 2013); perfusion and extracellular volume in rheumatoid arthritis (Hodgson et al., 2007); and cerebral perfusion and blood-brain barrier (BBB) permeability (Tofts, 1996; Nagaraja et al., 2011; Kellner et al., 2014). Gd-DOTA shows rapid and passive extravascular diffusion in the interstitial space without intracellular penetration, followed by a rapid urinary excretion via glomerular filtration (Le Mignon et al., 1990). Gd-DOTA does not cross the blood brain barrier in the healthy brain tissue.
It is plausible that gallium ion (Ga3+) labeled DOTA acts similarly in the body. [67Ga]DTPA has been used to measure passive BBB permeability in rat autoradiography studies (Uehara et al., 1997; Miyagawa et al., 1998, 2003). [64Cu]DOTA could be used to assess myocardial extracellular volume and fibrosis (Kim et al., 2016).
NODAGA and HBED-CC are alternative bifunctional chelating agents for 68Ga3+. NODAGA has faster labelling kinetics, and 68Ga3+ labelling is possible in room temperature (Kumar et al., 2018).
[68Ga]DOTA as perfusion tracer
Autio et al (2014) have used [68Ga]DOTA as a perfusion tracer in dynamic PET studies of rats. Studies were analyzed using one-tissue compartmental model, similar to the compartmental model for radiowater. The estimated K1 was at the same level as blood flow measured using radiowater in inflamed and normal tissue. Blood flow and [68Ga]DOTA K1 were clearly higher in inflamed tissue than in normal tissue. K1/k2 ratio may be another parameter of interest since it represents the extracellular volume, and vascular permeability in the brain.
[68Ga]DOTA could also be used to measure pulmonary blood flow (Velasco et al., 2017).
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Created at: 2014-12-19
Updated at: 2018-09-26
Written by: Vesa Oikonen