Biodistribution and clearance of 99mTc-labeled Arg-Gly-Asp (RGD) peptide in rats with ischemic acute renal failure.
Based on the previous demonstration of a renoprotective effect of arginine-glycine-aspartic acid (RGD) peptides in acute renal failure, experiments were designed to test the distribution and renal accumulation of the peptide. To accomplish this goal, in this study, RGD peptide was radiolabeled and its biodistribution and renal accumulation was determined in rats with ischemic acute renal failure (ARF). 99mTc-RGD with or without 111In-DTPA were injected intravenously in control and ARF rats. Various organs were dissected at different times after injection and subjected to gamma-scintillation counting and autoradiography (ARG). Blood clearance of 99mTc-RGD was rapid, with t1/2 < 10 min, and unchanged in ARF compared with control rats. Kidneys retained the largest portion of the injected dose in both control and ARF rats, as detected using scintillation counting and whole-body ARG (10.56 +/- 1.05% and 10.12 +/- 3.16% injected dose/g wet weight, respectively). Renal ARG revealed a significant increase in binding to the cortex in ARF kidneys, compared with that of control kidneys. Given the differences in renal blood flow and GFR in control and postischemic kidneys, the next series of experiments was performed with two radiopharmaceuticals, 99mTc-RGD and 111In-DTPA. The ratio of 99mTc-RGD:111In-DTPA was increased more than three-fold in ARF kidneys compared with control kidneys (2.7 +/- 0.15 versus 0.8 +/- 0.19, respectively). The results indicate that (1) RGD peptide undergoes a rapid clearance predominantly via the renal route; (2) despite a significant reduction in the renal perfusion, 99mTc-RGD peptide accumulates in the postischemic kidney; (3) this is consistent with the hypothesis on the involvement of RGD-recognizing integrins in the development of tubular obstruction in renal ischemia.
Noiri
E
E
Department of Medicine, State University of New York at Stony Brook 11794, USA.
Goligorsky
M S
MS
Wang
G J
GJ
Wang
J
J
Cabahug
C J
CJ
Sharma
S
S
Rhodes
B A
BA
Som
P
P
D058186:Acute Kidney Injury / Q000000981:diagnostic imaging / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D016023:Integrins / Q000378:metabolism; D007511:Ischemia / Q000000981:diagnostic imaging / Q000378:metabolism; D007668:Kidney / Q000098:blood supply; D008297:Male; D008657:Metabolic Clearance Rate; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D004369:Pentetic Acid / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D013667:Technetium / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D007205:Indium Radioisotopes; D016023:Integrins; D009842:Oligopeptides; D013667:Technetium; C047981:arginyl-glycyl-aspartic acid; D004369:Pentetic Acid