Abstract:F-1 exhibited a high specificity for the kidney, rapid renal excretion comparable to that of I-OIH and high in vivo radiochemical stability. Not only isF-1 a promising PET renal tracer, but it provides a route to the development of a pair of analogous F/Tc renal imaging agents with almost identical structures and comparable pharmacokinetic properties. These promising in vivo results warrant subsequent evaluation in humans.
“…The PET images were first co-registered to the CT images. Partial regions of interest were drawn on the CT images of a selection of mouse organs: brain, heart, lungs, liver, muscle, large intestine, and bone marrow to obtain the activity concentration in 17 measured time-points after injection (0, 5,10,15,20,25,30,35,40,45,50,55,60,65,70,75, 80 and 85 min). Whole-organ contours were drawn to measure the activity in the kidneys and bladder of the mice.…”
para-Aminobenzoic acid (PABA) has been previously used as an exogenous marker to verify completion of 24-hour urine sampling. Therefore, we hypothesized that radiolabeled PABA with 11 C could allow high-quality dynamic PET of the kidneys while reducing the radiation exposure due to its short biological and physical half-lives. We evaluated if 11 C-PABA could visualize renal anatomy and quantify function in healthy rats, rabbits, and first-inhuman studies in healthy volunteers. Methods: Healthy rats and rabbits were injected with 11 C-PABA intravenously. Subsequently, a dynamic PET was performed followed by post-mortem tissue biodistribution studies. 11 C-PABA PET was directly compared with the current standard, 99m Tc-MAG3 in rats. Three healthy human subjects also underwent dynamic PET after intravenous injection of 11 C-PABA. Results: In healthy rats and rabbits, dynamic PET demonstrated a rapid accumulation of 11 C-PABA in the renal cortex, followed by rapid excretion through the pelvicalyceal system. In humans, 11 C-PABA PET was safe and well tolerated. There were no adverse or clinically detectable pharmacologic effects in any subject. The cortex was delineated on PET, and the activity gradually transited to the medulla and then renal pelvis with high spatiotemporal resolution. Conclusion: 11 C-PABA demonstrated fast renal excretion with very low background signal in animals and humans. These results suggest that 11 C-PABA could be used as a novel radiotracer for functional renal imaging, providing high-quality spatiotemporal images with low radiation exposure.
“…The PET images were first co-registered to the CT images. Partial regions of interest were drawn on the CT images of a selection of mouse organs: brain, heart, lungs, liver, muscle, large intestine, and bone marrow to obtain the activity concentration in 17 measured time-points after injection (0, 5,10,15,20,25,30,35,40,45,50,55,60,65,70,75, 80 and 85 min). Whole-organ contours were drawn to measure the activity in the kidneys and bladder of the mice.…”
para-Aminobenzoic acid (PABA) has been previously used as an exogenous marker to verify completion of 24-hour urine sampling. Therefore, we hypothesized that radiolabeled PABA with 11 C could allow high-quality dynamic PET of the kidneys while reducing the radiation exposure due to its short biological and physical half-lives. We evaluated if 11 C-PABA could visualize renal anatomy and quantify function in healthy rats, rabbits, and first-inhuman studies in healthy volunteers. Methods: Healthy rats and rabbits were injected with 11 C-PABA intravenously. Subsequently, a dynamic PET was performed followed by post-mortem tissue biodistribution studies. 11 C-PABA PET was directly compared with the current standard, 99m Tc-MAG3 in rats. Three healthy human subjects also underwent dynamic PET after intravenous injection of 11 C-PABA. Results: In healthy rats and rabbits, dynamic PET demonstrated a rapid accumulation of 11 C-PABA in the renal cortex, followed by rapid excretion through the pelvicalyceal system. In humans, 11 C-PABA PET was safe and well tolerated. There were no adverse or clinically detectable pharmacologic effects in any subject. The cortex was delineated on PET, and the activity gradually transited to the medulla and then renal pelvis with high spatiotemporal resolution. Conclusion: 11 C-PABA demonstrated fast renal excretion with very low background signal in animals and humans. These results suggest that 11 C-PABA could be used as a novel radiotracer for functional renal imaging, providing high-quality spatiotemporal images with low radiation exposure.
“…However, novel PET radiotracers, such as [ 68 Ga]EDTA, [ 18 F]FDS and Re(CO) 3 ([ 18 F]FEDA), may have superior pharmacokinetic profiles, mainly due to low plasma protein binding and high metabolic stability (Fig. 1) [6, 14, 17]. Fig.…”
Section: Comparison Of Pet Single-photon Planar Imaging and Spect Inmentioning
confidence: 99%
“…Based on these encouraging results, the authors demonstrated similar findings by developing an efficient, one-step radiosynthesis of an 18 F-Re-tricarbonyl PET tracer, namely Re(CO) 3 ([ 18 F]FEDA). Re(CO) 3 ([ 18 F]FEDA) shows high renal specificity, high in vitro and in vivo stability and rapid renal excretion, which are comparable to those of its analogue [ 99m Tc](CO) 3 (FEDA) [17]. The pharmacokinetic properties of Re(CO) 3 ([ 18 F]FEDA) are also comparable to those of [ 131 I]OIH, which is considered the reference standard for ERPF measurement [17, 42].…”
Section: F-labelled Radiotracers For Renal Function Imagingmentioning
confidence: 99%
“…In contrast to conventional molecular imaging modalities, positron emission tomography (PET) radiotracers for renal functional assessment offer several key advantages, such as better spatiotemporal resolution, absolute camera-based quantification, and rapid three-dimensional imaging. In this regard, multiple renal PET radiotracers to assess renal function are currently under investigation, including [ 68 Ga]EDTA, [ 18 F]Re(CO) 3 - N -(fluoroethyl)iminodiacetic acid (Re(CO) 3 ([ 18 F]FEDA)), and 2-deoxy-2-[ 18 F]fluorosorbitol ([ 18 F]FDS) [14–17] (Fig. 1).…”
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.
“…Imaging of specific molecular targets, such as CD206 within the glomerulus and the organic anion transporter 1 of proximal tubules (45,46), represents a complementary strategy for the noninvasive measurement of renal function. Both targets are energy-dependent transporters of physiologically significant molecules at 2 critical cell types that serve different functions within the kidney.…”
Section: Optimization Of the Molecular Imaging Agentmentioning
An unmet need for the clinical management of chronic kidney disease is a predictive tool of kidney function during the first decade of the disease, when there is silent loss of glomerular function. The objective of this study was to demonstrate receptormediated binding of tilmanocept to CD206 within the kidney and provide evidence of kinetic sensitivity of this binding to renal function. Methods: Rats were positioned in a PET scanner with the liver and kidneys within the field of view. After an intravenous injection of 68 Ga-IRDye800-tilmanocept, using 1 of 2 scaled molar doses (0.02 nmol/g, n 5 5; or 0.10 nmol/g, n 5 5), or coinjection (n 5 3) of 68 Ga-IRDye800-tilmanocept (0.10 nmol/g) and unlabeled tilmanocept (5.0 nmol/g), or a negative control, 68 Ga-IRDye800-DTPA-galactosyl-dextran (0.02 nmol/g, n 5 5), each animal was imaged for 20 min followed by a whole-body scan. Frozen kidney sections were stained for podocytes and CD206 using immunofluorescence. Molecular imaging of diabetic db/db mice (4.9 wk, n 5 6; 7.3 wk, n 5 4; 13.3 wk, n 5 6) and nondiabetic db/m mice (n 5 6) was performed with fluorescence-labeled 99m Tc-tilmanocept (18.5 MBq, 2.6 nmol). Thirty minutes after injection, blood, liver, kidneys, and urine were assayed for radioactivity. Renal time-activity curves were generated. Results: Rat PET whole-body images and time-activity curves of 68 Ga-IRDye800-tilmanocept demonstrated receptor-mediated renal accumulation with evidence of glomerular uptake. Activity within the renal cortex persisted during the 40-min study. Histologic examination demonstrated colocalization of CD206 and IRDye800-tilmanocept within the glomerulus. The glomerular accumulation of the coinjection and the negative control studies were significantly less than the CD206-targeted agent. The db/db mice displayed a multiphasic renal time-activity curve with high urinary bladder accumulation; the nondiabetic mice exhibited renal uptake curves dominated by a single phase with low bladder accumulation. Conclusion: This study demonstrated receptor-mediated binding to the glomerular mesangial cells and kinetic sensitivity of tilmanocept to chronic renal disease. Given the role of mesangial cells during the progression of diabetic nephropathy, PET or SPECT renal imaging with radiolabeled tilmanocept may provide a noninvasive quantitative assessment of glomerular function.
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