Abstract
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 18F-labelled and 68Ga-labelled agents. Several reported PET imaging probes allow assessment of glomerular filtration rate, such as [68Ga]ethylenediaminetetraacetic acid ([68Ga]EDTA), [68Ga]IRDye800-tilmanocept and 2-deoxy-2-[18F]fluorosorbitol ([18F]FDS)). The diagnostic performance of [68Ga]EDTA has already been demonstrated in a clinical trial. [68Ga]IRDye800-tilmanocept shows receptor-mediated binding to glomerular mesangial cells, which in turn may allow the monitoring of progression of diabetic nephropathy. [18F]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-[18F]fluoro-d-glucose, [18F]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-([18F]fluoroethyl)iminodiacetic acid (Re(CO)3([18F]FEDA)). This compound demonstrates similar pharmacokinetic properties to its 99mTc-labelled analogue [99mTc](CO)3(FEDA). Thus, if there is a shortage of molybdenum-99, Re(CO)3([18F]FEDA would allow direct comparison with previous studies with 99mTc. 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.
Highlights
Glomerular filtration rate (GFR) is defined as the rate of plasma flow through the glomerulus into the urinary space of the Bowman’s capsule and is the most suitable index and key indicator for renal function
A shift from single-photon-emitting to positron emission tomography (PET) radiotracers has occurred in a variety of clinical settings [58,59,60], and the concept of PET has been applied to renal radionuclide imaging
Several novel PET radiotracers for the assessment of renal function are currently emerging: the GFR-reflecting PET probes [68Ga]EDTA, [68Ga]IRDye800-tilmanocept and [18F]FDS, and the tubular agent Re(CO)3([18F]FEDA) [6, 13,14,15, 17, 27]. [68Ga]EDTA is the only agent to date that has already been evaluated in a large clinical trial [13]. [68Ga]IRDye800tilmanocept shows receptor-mediated binding to glomerular mesangial cells, which in turn may allow monitoring of progression of diabetic nephropathy [27]
Summary
Glomerular filtration rate (GFR) is defined as the rate of plasma flow through the glomerulus into the urinary space of the Bowman’s capsule and is the most suitable index and key indicator for renal function. The lack of radiolabelled metabolites in the blood and urine 35 min after injection was confirmed by thin-layer radiochromatography This feasibility study in healthy rats suggested that [18F]FDS is freely filtered at the renal glomerulus, and this is in line with previous findings showing rapid clearance of exogenous administered sorbitol that is identical to inulin clearance, as measured in dogs and humans. In a study by Geist et al [47], 24 healthy volunteers underwent [18F]FDG dynamic PET/magnetic resonance imaging, and Patlak analysis was performed to determine GFR and ERPF These quantitative indices correlated with both [99mTc]MAG3 tubular extraction rate and blood-based creatinine clearance in an acceptable range (R = 0.73–0.78).
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