Diagnostic imaging of the kidneys for the determination of renal function.
In the U.S., approximately eight million adults have kidney disease. In order to diagnose and treat renal diseases and disorders, it is essential to measure glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and the filtration fraction (GFR/ERPF). The best performing compound for measuring ERPF has been the compound para-aminohippurate (PAH). However, assaying PAH requires a laboratory-based biochemical assay. In order to allow physicians to more quickly and effectively determine renal plasma flow, diagnostic imaging companies have developed and marketed various radiolabeled renal tracers for the measurement of ERPF. For several years, 131I-ortho-iodohippurate (131I-OIH) has been the gold standard radiolabeled renal tracer. However, this tracer is no longer on the market in the U.S. For imaging purposes, the renal tracer technetium-99m mercaptoacetyltriglycine (99mTc-MAG3) has now replaced 131I-OIH as an agent available to physicians for clinical use. However, for measuring ERPF, 99mTc-MAG3 is far from optimal as its clearance is only 50-60% that of 131I-OIH. In addition, studies have indicated that there is a wide variation in 99mTc-MAG3 clearance, which may make the accurate estimation of the renal plasma flow using this tracer difficult. 99mTc-LL-ethylene dicysteine and 99mTc-DD-ethylene dicysteine are additional ERPF renal tracers. While both compounds have higher clearance than 99mTc-MAG3, their clearance is still only about 60-65% of that of PAH.
This technology provides an improved renal tracer for determining ERPF, which has clearance characteristics that are superior to currently available tracers. The tracer, a small molecule radiolabeled with technetium-99m, is stable, exists as a single species and is amenable to formulation in a kit. In vivo studies in rats indicate that the pharmacokinetics of the tracer are essentially identical to those of 131I-OIH. In addition, preliminary studies in normal human volunteers suggest that the pharmacokinetic behavior of the 99mTc-labeled compound is also comparable to that of 131I-OIH.
Proof-of-principle study has been conducted in human volunteers with image quality and renogram parameters comparable to those of 131I-OIH.