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001-es BibID:BIBFORM004323
Első szerző:Balogh Lajos
Cím:Absorption, uptake and tissue affinity of high-molecular-weight hyaluronan after oral administration in rats and dogs / Lajos Balogh, Andras Polyak, Domokos Mathe, Reka Kiraly, Juliana Thuroczy, Marian Terez, Gyozo Janoki, Yaoting Ting, Luke R. Bucci, Alexander G. Schauss
Dátum:2008
Megjegyzések:The purpose of this study was to determine the absorption, distribution and excretion of (99m)technetium-labeled, high-molecular-weight hyaluronan (((99m)Tc-HA) and (99m)technetium pertechnetate ((99m)Tc-P) after single dose, oral administration to Wistar rats and Beagle dogs. A pilot study utilized (99m)Tc-HA alone, and a second confirmatory study compared uptake of labeled (99m)Tc-HA with (99m)Tc-P. Urinary and fecal excretion after (99m)Tc-HA ingestion by rats showed 86.7-95.6% of radioactivity was recovered, almost all in feces. All tissues examined showed incorporation of radioactivity from (99m)Tc-HA starting at 15 min and persisting for 48 h, in a pattern significantly different from (99m)Tc-P. Whole-body scintigraphs and close-ups of the ventral chest region showed nonalimentary radioactivity from (99m)Tc-HA concentrated in joints, vertebrae and salivary glands four hours after administration. Autoradiography of skin, bone and joint tissue pieces after 24 h showed incorporation of radioactivity from (99m)Tc-HA, but not from (99m)Tc-P. Conversely, absorption, distribution and excretion of (99m)Tc was completely different from (99m)Tc-HA, showing an expected pattern of rapid absorption and excretion in urine, with accumulation in thyroid glands, stomach, kidney and bladder. This report presents the first evidence for uptake and distribution to connective tissues of orally administered, high-molecular-weight HA.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Journal of Agricultural and Food Chemistry. - 56 : 22 (2008), p. 10582-10593. -
További szerzők:Polyák András Máthé Domokos Király Réka Thuróczy Julianna Márián Teréz (1950-) (radiobiológus) Jánoki Győző Ting, Yaoting Bucci, R. Luke Schauss, Alexander G.
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001-es BibID:BIBFORM019426
Első szerző:Máthé Domokos
Cím:Multispecies animal investigation on biodistribution, pharmacokinetics and toxicity of 177Lu-EDTMP, a potential bone pain palliation agent / Máthé D., Balogh L., Polyák A., Király R., Márián T., Pawlak D., Zaknun J. J., Pillai M. R., Jánoki G. A.
Dátum:2010
ISSN:0969-8051
Megjegyzések:Radionuclide therapy (RNT) is an effective method for bone pain palliation in patients suffering from bone metastasis. Due to the long half-life, easy production and relatively low beta- energy, (177)Lu [T(1/2)=6.73 days, E(beta max)=497 keV, E(gamma)=113 keV (6.4%), 208 keV (11%)]-based radiopharmaceuticals offer logistical advantage for wider use. This paper reports the results of a multispecies biodistribution and toxicity studies of (177)Lu-EDTMP to collect preclinical data for starting human clinical trials. METHODS: (177)Lu-EDTMP with radiochemical purity greater than 99% was formulated by using a lyophilized kit of EDTMP (35 mg of EDTMP, 5.72 g of CaO and 14.1 mg of NaOH). Biodistribution studies were conducted in mice and rabbits. Small animal imaging was performed using NanoSPECT/CT (Mediso, Ltd., Hungary) and digital autoradiography. Gamma camera imaging was done in rabbits and dogs. Four levels of activity (9.25 through 37 MBq/kg body weight) of (177)Lu-EDTMP were injected in four groups of three dogs each to study the toxicological effects. RESULTS: (177)Lu-EDTMP accumulated almost exclusively in the skeletal system (peak ca. 41% of the injected activity in bone with terminal elimination half-life of 2130 and 1870 h in mice and rabbits, respectively) with a peak uptake during 1-3 h. Excretion of the radiopharmaceutical was through the urinary system. Imaging studies showed that all species (mouse, rat, rabbit and dog) take up the compound in regions of remodeling bone, while kidney retention is not visible after 1 day postinjection (pi). In dogs, the highest applied activity (37 MBq/kg body weight) led to a moderate decrease in platelet concentration (mean, 160 g/L) at 1 week pi with no toxicity. CONCLUSION: The protracted effective half-life of (177)Lu-EDTMP in bone supports that modifying the EDTMP molecule by introducing (177)Lu does not alter its biological behaviour as a specific bone-seeking tracer. Species-specific pharmacokinetic behavior differences were observed. Toxicity studies in dogs did not show any biological adverse effects. The studies demonstrate that (177)Lu-EDTMP is a promising radiopharmaceutical that can be further evaluated for establishing as a radiopharmaceutical for human use.
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Nuclear Medicine and Biology. - 37 : 2 (2010), p. 215-226. -
További szerzők:Balogh Lajos Polyák András Király Réka Márián Teréz (1950-) (radiobiológus) Pawlak, Dariusz Zaknun, John J. Pillai, M. R. Jánoki Győző
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