The next era of renal radionuclide imaging: novel PET radiotracers

Although single-photon-emitting radiotracers have long been the standard for renal functional molecular imaging, recent years have seen the development of positron emission tomography (PET) agents for this application. We provide an overview of renal radionuclide PET radiotracers, in particular focusing on novel ${}^{18}$F-labelled and ${}^{68}$Ga-labelled agents. Several reported PET imaging probes allow assessment of glomerular filtration rate, such as [${}^{68}$Ga]ethylenediaminetetraacetic acid ([${}^{68}$Ga]EDTA), [${}^{68}$Ga]IRDye800-tilmanocept and 2-deoxy-2-[${}^{18}$F]fluorosorbitol ([${}^{18}$F]FDS)). The diagnostic performance of [${}^{68}$Ga]EDTA has already been demonstrated in a clinical trial. [${}^{68}$Ga]IRDye800-tilmanocept shows receptor-mediated binding to glomerular mesangial cells, which in turn may allow the monitoring of progression of diabetic nephropathy. [${}^{18}$F]FDS shows excellent kidney extraction and excretion in rats and, as has been shown in the first study in humans. Further, due to its simple one-step radiosynthesis via the most frequently used PET radiotracer 2-deoxy-2-[${}^{18}$F]fluoro-d-glucose, [${}^{18}$F]FDS could be available at nearly every PET centre. A new PET radiotracer has also been introduced for the effective assessment of plasma flow in the kidneys: Re(CO)${}_3$-N-([${}^{18}$F]fluoroethyl)iminodiacetic acid (Re(CO)${}_3$([${}^{18}$F]FEDA)). This compound demonstrates similar pharmacokinetic properties to its ${}^{99m}$Tc-labelled analogue [${}^{99m}$Tc](CO)3(FEDA). Thus, if there is a shortage of molybdenum-99, Re(CO)${}_3$([${}^{18}$F]FEDA would allow direct comparison with previous studies with ${}^{99m}$Tc. The PET radiotracers for renal imaging reviewed here allow thorough evaluation of kidney function, with the tremendous advantage of precise anatomical coregistration with simultaneously acquired CT images and rapid three-dimensional imaging capability.