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Absorption, distribution, excretion and tissue uptake of 99mtechnetium labeled hyaluronan (HA) after single oral doses in rats and beagle dogs
Author(s) -
Schauss Alexander G,
Balogh Lajos,
Polyak Andras,
Mathe Domokos,
Kiraly Reka,
Gyozo Janoki,
Yao Tingting,
Bucci Luke R
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.729
Subject(s) - beagle , excretion , urine , chemistry , absorption (acoustics) , connective tissue , thyroid , distribution (mathematics) , endocrinology , medicine , feces , pertechnetate , urinary system , technetium , pathology , biology , biochemistry , mathematical analysis , mathematics , paleontology , physics , nuclear chemistry , acoustics
High‐molecular weight HA (HyaMax®, 1 MDa) labeled with 99m Technetium ( 99m Tc‐HA) or free 99m Technetium pertechnetate ( 99m Tc) administered to rats/dogs per os. Distribution of radioactivity in blood & tissues of rats was determined at 5,15,30 mins, 1,2,4,6,12,24,48,72 hrs. Urinary & fecal excretion determined in rats at 12,24,48,72 hrs. Blood & urinary clearance determined in dogs. Scintigraphic imaging, autoradiography of tissue pieces & SPECT/CT scans evaluated tissue uptake in rats. 99m Tc‐HA was labeled with 85% efficiency & stable for >48 hrs. Blood levels of radioactivity for 99m Tc‐HA peaked 2–4 hrs in rats/dogs. Most tissues examined showed incorporation of radioactivity at 15 mins up to 48 hrs. After 72 hrs, 86.7% of radioactivity from 99m Tc‐HA recovered, almost all in feces; 94.4% from 99m Tc, almost all from urine. Autoradiography showed incorporation of radioactivity from 99m Tc‐HA, but not free 99m Tc, in skin, bones & joints at 24 hrs. Absorption/distribution of free 99m Tc was completely different from 99m Tc‐HA, showing a pattern of rapid absorption & excretion, with accumulation in thyroid glands, & removal via urine. Control experiments indicated radioactivity in tissues after 99m Tc‐HA not due to free 99m Tc‐HA. Shows evidence for uptake of 13.3% of oral dose of high‐molecular‐weight HA, with accumulation in connective tissues. Supported by Fenchem Biotek and Schiff Nutrition International.