Radiolabelled autologous low density lipoprotein (LDL) has previously been used to study in vivo distribution and metabolism of native-LDL. Non-invasive imaging of atherosclerotic lesions using Tc-99m-LDL was shown to be feasible in animal models and patients but the clinical utility remains to be assessed. Since recent reports suggest that oxidized LDL may play a major role in the pathogenesis of atherosclerosis, we developed a technique to oxidize autologous LDL and compared the biodistribution of oxidized-LDL with that of native-LDL in man. In addition, we evaluated the uptake in vivo of oxidized- and native-LDL by atherosclerotic plaques. LDL, obtained from human plasma was treated with various combinations of copper ions and H2O2 to induce oxidative modification by increasing the content of lipid peroxidation products and electrophoretic mobility. When LDL (0.3 mg/ml) was incubated with 100 mu M Cu2+ and 500 mu M H2O2 oxidation occurred rapidly within 1 h, and was labelled with Tc-99m efficiently as native LDL. In vivo distribution studies revealed a faster plasma clearance of oxidized-LDL compared to native-LDL, and a higher uptake by the reticuloendothelial system. Tomographic scintigraphy of the neck in patients suffering from transient ischemic attacks, revealed accumulation of radiolabelled LDL preparations in the carotid artery affected by atherosclerotic lesions. We developed a technique to rapidly oxidize LDL using copper and H2O2. Biodistribution data demonstrate that oxidized-LDL is rapidly cleared from circulation, is taken up mostly by organs rich in macrophages, and can be detected at the level of carotid plaques.

Preparation and biodistribution of (99m)technetium labelled oxidized LDL in man / Iuliano, Luigi; Signore, Alberto; Shankar, Vallabajosula; Angela R., Colavita; Caterina, Camastra; Ronga, Giuseppe; Alessandri, Cesare; Sbarigia, Enrico; Fiorani, Paolo; Violi, Francesco. - In: ATHEROSCLEROSIS. - ISSN 0021-9150. - STAMPA. - 126:1(1996), pp. 131-141. [10.1016/0021-9150(96)05888-1]

Preparation and biodistribution of (99m)technetium labelled oxidized LDL in man

IULIANO, Luigi;SIGNORE, Alberto;RONGA, Giuseppe;ALESSANDRI, Cesare;SBARIGIA, Enrico;FIORANI, Paolo;VIOLI, Francesco
1996

Abstract

Radiolabelled autologous low density lipoprotein (LDL) has previously been used to study in vivo distribution and metabolism of native-LDL. Non-invasive imaging of atherosclerotic lesions using Tc-99m-LDL was shown to be feasible in animal models and patients but the clinical utility remains to be assessed. Since recent reports suggest that oxidized LDL may play a major role in the pathogenesis of atherosclerosis, we developed a technique to oxidize autologous LDL and compared the biodistribution of oxidized-LDL with that of native-LDL in man. In addition, we evaluated the uptake in vivo of oxidized- and native-LDL by atherosclerotic plaques. LDL, obtained from human plasma was treated with various combinations of copper ions and H2O2 to induce oxidative modification by increasing the content of lipid peroxidation products and electrophoretic mobility. When LDL (0.3 mg/ml) was incubated with 100 mu M Cu2+ and 500 mu M H2O2 oxidation occurred rapidly within 1 h, and was labelled with Tc-99m efficiently as native LDL. In vivo distribution studies revealed a faster plasma clearance of oxidized-LDL compared to native-LDL, and a higher uptake by the reticuloendothelial system. Tomographic scintigraphy of the neck in patients suffering from transient ischemic attacks, revealed accumulation of radiolabelled LDL preparations in the carotid artery affected by atherosclerotic lesions. We developed a technique to rapidly oxidize LDL using copper and H2O2. Biodistribution data demonstrate that oxidized-LDL is rapidly cleared from circulation, is taken up mostly by organs rich in macrophages, and can be detected at the level of carotid plaques.
1996
accumulation; apolipoprotein-b; atherogenesis; atherosclerosis; foam cells; free radicals; human atherosclerosis; imaging; ldl-biodistribution; lipid-peroxidation; lipoproteins; low-density lipoprotein; macrophages; malondialdehyde; oxidized-ldl; rabbit arterial-wall
01 Pubblicazione su rivista::01a Articolo in rivista
Preparation and biodistribution of (99m)technetium labelled oxidized LDL in man / Iuliano, Luigi; Signore, Alberto; Shankar, Vallabajosula; Angela R., Colavita; Caterina, Camastra; Ronga, Giuseppe; Alessandri, Cesare; Sbarigia, Enrico; Fiorani, Paolo; Violi, Francesco. - In: ATHEROSCLEROSIS. - ISSN 0021-9150. - STAMPA. - 126:1(1996), pp. 131-141. [10.1016/0021-9150(96)05888-1]
File allegati a questo prodotto
File Dimensione Formato  
Iuliano_Preparation and biodistribution_1996.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 783.48 kB
Formato Adobe PDF
783.48 kB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/469667
Citazioni
  • ???jsp.display-item.citation.pmc??? 13
  • Scopus 79
  • ???jsp.display-item.citation.isi??? 70
social impact