The next era of renal radionuclide imaging: novel PET radiotracers

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 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.

11C-PABA as a PET Radiotracer for Functional Renal Imaging: Preclinical and First-in-Human Study

“…Volumes of interest derived by PET studies that cover "areas at risk" in the renal cortex or medulla may allow monitoring of renal injury after radiation or may even have predictive potential prior to therapy. Given these benefits, several PET radiotracers have been evaluated for renal imaging with promising results (2,7). With the benefits of a longer radiological half-life, 18 F-FDS has also been recently evaluated as a potential renal imaging agent (as a replacement for 99m Tc-DTPA) in healthy and diseased rats as well as healthy human subjects (24)(25)(26).…”

“…While these techniques are still widely used in clinical practice, they have some major limitations including two-dimensional information with a concomitant lack of accurate anatomic correlation, low spatial resolution, and low signal/background ratios. The soft-tissue attenuation may also reduce diagnostic accuracy and limit reliable quantification (2). Implementation of single-photon emission computed tomography (SPECT) for renal imaging led to improvements in image contrast and spatial resolution.…”

“…Consequently, PET requires administration of much lower doses of radioactivity and provides higher accuracy measurements of regional radiopharmaceutical tissue concentrations (2)(3)(4).…”

The increasing potential of nuclear medicine imaging for the evaluation and reduction of normal tissue toxicity from radiation treatments

“…Most recently, 99m Tc-MAG3 SPECT was used to assess dynamic renal changes from 177 Lu-DOTA-TATE therapy in mice [38]. Recent years have also seen the development of new renal PET tracers, such as [ 68 Ga]Ga-EDTA and [ 18 F]fluorosorbitol (FDS), which allow for imaging with better resolution and quantification [63]. Assessment aside, strategies to reduce kidney toxicity in PSMA therapy have also been developed and tested.…”

PAMAM Dendrimer‐Based Nanodevices for Nuclear Medicine Applications

“…PET imaging has attracted growing interest for accurate diagnosis, prognosis evaluation, and therapy monitoring due to its excellent sensitivity and quantitative measurement property. A great variety of positron‐emitting isotopes that can be classified into radiometals (e.g., 64 Cu, 68 Ga, and 89 Zr) and non‐metals (e.g., 11 C, 13 N, 15 O, and 18 F) become available for PET imaging . These isotopes show distinct decay time ranging from a few minutes to hundreds of days depending on their intrinsic physicochemical properties.…”