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

Abstract

para-Aminobenzoic acid (PABA) has been previously used as an exogenous marker to verify completion of 24-h urine sampling. Therefore, we hypothesized that PABA radiolabeled with ¹¹C might allow high-quality dynamic PET of the kidneys with less radiation exposure than other agents because of its shorter biologic and physical half-life. We evaluated if ¹¹C-PABA can visualize renal anatomy and quantify function in healthy rats and rabbits and in a first-in-humans study on healthy volunteers. Methods: Healthy rats and rabbits were injected with ¹¹C-PABA intravenously. Subsequently, dynamic PET was performed, followed by postmortem tissue-biodistribution studies. ¹¹C-PABA PET was directly compared with the current standard, ^99mTc-mercaptoacetyltriglycin, in rats. Three healthy human subjects also underwent dynamic PET after intravenous injection of ¹¹C-PABA. Results: In healthy rats and rabbits, dynamic PET demonstrated a rapid accumulation of ¹¹C-PABA in the renal cortex, followed by rapid excretion through the pelvicalyceal system. In humans, ¹¹C-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 pelvis with high spatiotemporal resolution. Conclusion:¹¹C-PABA demonstrated fast renal excretion with a very low background signal in animals and humans. These results suggest that ¹¹C-PABA might be used as a novel radiotracer for functional renal imaging, providing high-quality spatiotemporal images with low radiation exposure.

Keywords: PABA; PET; renal imaging; renography; translational science.

Graphical abstract

FIGURE 1.

¹¹C-PABA PET/CT renal imaging in healthy rats. (A) Coronal dynamic ¹¹C-PABA PET images of right kidney from representative rat show rapid cortical uptake after 2 min, followed by rapid clearance through pelvicalyceal system. (B) Maximum-intensity-projection ¹¹C-PABA PET/CT images show abdominal aorta and iliac arteries 60 s after injection, as well as high activity in bladder (Bl) after 20 min, with low background signal in other tissues. (C) Average ¹¹C-PABA time–activity curves for kidneys and bladder. Data are mean (solid lines) and SD (shaded areas) (n = 4). %ID = percentage injected dose.

FIGURE 2.

¹¹C-PABA and ^99mTc-MAG3 tissue biodistribution in rats. Healthy rats received simultaneous intravenous injections of ¹¹C-PABA and ^99mTc-MAG3 and were killed 30 min afterward. ^99mTc-MAG3 counts were determined 2 h after ¹¹C-PABA counts, when signal from ¹¹C (physical half-life, 20 min) would have completely decayed. (A) Biodistribution of ¹¹C-PABA was primarily within kidneys, with very low activity in all other measured organs. (B) Conversely, biodistribution of ^99mTc-MAG3 had higher background activity. Data are mean and SD (n = 4).

FIGURE 3.

¹¹C-PABA PET/CT renal imaging in healthy rabbits. (A) Coronal dynamic ¹¹C-PABA PET/CT images of right kidney of representative rabbit show rapid delineation of renal cortex and then accumulation in pelvicalyceal system. (B) Maximum-intensity-projection ¹¹C-PABA PET/CT image at 20 min shows similar uptake in left and right kidneys, with low background signal in other organs. (C) Average ¹¹C-PABA time–activity curves for kidneys. Data are mean (n = 2). %ID = percentage injected dose.

FIGURE 4.

¹¹C-PABA PET renal imaging in healthy human subjects. (A) Maximum-intensity-projection ¹¹C-PABA PET/CT images of representative subject. Vascular phase is observed starting 22 s after injection, demonstrating renal perfusion. Cortical uptake phase is evident within 2.7 and 3.2 min, with maximal parenchymal uptake in renal cortex. Excretory phase is seen after 9 min, indicating maximal uptake in pelvicalyceal system. (B) Average ¹¹C-PABA time–activity curves for kidneys and blood (aorta). Data are mean (solid lines) and SD (shaded areas) (n = 3).