Doubly radiolabeled liposomes for pretargeted radioimmunotherapy.
Identifieur interne : 002765 ( Main/Exploration ); précédent : 002764; suivant : 002766Doubly radiolabeled liposomes for pretargeted radioimmunotherapy.
Auteurs : RBID : pubmed:17592745English descriptors
- KwdEn :
- Animals, Arginine (chemistry), Drug Delivery Systems, Drug Stability, Female, Indicators and Reagents, Indium Radioisotopes, Iodine Radioisotopes, Isotope Labeling, Liposomes (chemistry), Liposomes (pharmacokinetics), Mice, Mice, Inbred BALB C, Radioimmunotherapy, Succinimides (chemistry), Tissue Distribution.
- MESH :
- chemical , chemistry : Arginine, Liposomes, Succinimides.
- chemical , pharmacokinetics : Liposomes.
- Animals, Drug Delivery Systems, Drug Stability, Female, Indicators and Reagents, Indium Radioisotopes, Iodine Radioisotopes, Isotope Labeling, Mice, Mice, Inbred BALB C, Radioimmunotherapy, Tissue Distribution.
Abstract
The aim of this study was to design liposomes as radioactivity carriers for pretargeted radioimmunotherapy with favorable pharmacokinetic parameters. To monitor the liposomes integrity in vivo, their surface was radiolabeled with indium-111 bound to DTPA-derivatized phosphatidylethanolamine (DSPE-DTPA) and the aqueous phase was labeled by using an original active loading technique of radioiodinated Bolton-Hunter reagent (BH) that reacts with pre-encapsulated arginine to form a positively charged conjugate ((125)I-BH-arginine). Different formulations of doubly radiolabeled liposomes were tested in vitro and in vivo to evaluate radiolabeling stability, integrity of the vesicles and their pharmacokinetics. Radiolabeling yields were high (surface >75%, encapsulation >60%) and stable (>85% after 24 h in serum 37 degrees C). In vivo, the pharmacokinetic behavior of doubly radiolabeled liposomes was strongly dependant on the formulation. Blood clearance of PEGylated liposomes (DSPC/Chol/DSPE-DTPA/DSPE-PEG5%) was 0.15 mL/h compared to a conventional formulation (DSPC/Chol/DSPE-DTPA: clearance 1.44 mL/h). Non-encapsulated BH-arginine conjugate was quickly eliminated in urine (clearance 6.04 mL/h). Blood kinetics of the two radionuclides were similar and radiochromatographic profiles of mice serum confirmed the integrity of circulating liposomes. The significant reduction of activity uptake in organs after liposome catabolism (liver and spleen), achieved by the rapid renal elimination of (125)I-BH-arginine, should bring significant improvements for targeted radionuclide therapy with sterically-stabilized liposomes.
DOI: 10.1016/j.ijpharm.2007.05.024
PubMed: 17592745
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Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Doubly radiolabeled liposomes for pretargeted radioimmunotherapy.</title>
<author><name sortKey="Mougin Degraef, M" uniqKey="Mougin Degraef M">M Mougin-Degraef</name>
<affiliation wicri:level="3"><nlm:affiliation>Département de recherche en cancérologie, INSERM, U601, Université de Nantes, 9 quai Moncousu 44093, Nantes Cedex 1, France. marie.mougin@nantes.inserm.fr</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Département de recherche en cancérologie, INSERM, U601, Université de Nantes, 9 quai Moncousu 44093, Nantes Cedex 1</wicri:regionArea>
<placeName><region type="region" nuts="2">Pays de la Loire</region>
<settlement type="city">Nantes</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bourdeau, C" uniqKey="Bourdeau C">C Bourdeau</name>
</author>
<author><name sortKey="Jestin, E" uniqKey="Jestin E">E Jestin</name>
</author>
<author><name sortKey="Sai Maurel, C" uniqKey="Sai Maurel C">C Saï-Maurel</name>
</author>
<author><name sortKey="Bourgeois, M" uniqKey="Bourgeois M">M Bourgeois</name>
</author>
<author><name sortKey="Saec, P Remaud Le" uniqKey="Saec P">P Remaud-Le Saëc</name>
</author>
<author><name sortKey="Thedrez, P" uniqKey="Thedrez P">P Thédrez</name>
</author>
<author><name sortKey="Gestin, J F" uniqKey="Gestin J">J-F Gestin</name>
</author>
<author><name sortKey="Barbet, J" uniqKey="Barbet J">J Barbet</name>
</author>
<author><name sortKey="Faivre Chauvet, A" uniqKey="Faivre Chauvet A">A Faivre-Chauvet</name>
</author>
</titleStmt>
<publicationStmt><date when="2007">2007</date>
<idno type="doi">10.1016/j.ijpharm.2007.05.024</idno>
<idno type="RBID">pubmed:17592745</idno>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Arginine (chemistry)</term>
<term>Drug Delivery Systems</term>
<term>Drug Stability</term>
<term>Female</term>
<term>Indicators and Reagents</term>
<term>Indium Radioisotopes</term>
<term>Iodine Radioisotopes</term>
<term>Isotope Labeling</term>
<term>Liposomes (chemistry)</term>
<term>Liposomes (pharmacokinetics)</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Radioimmunotherapy</term>
<term>Succinimides (chemistry)</term>
<term>Tissue Distribution</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Arginine</term>
<term>Liposomes</term>
<term>Succinimides</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Liposomes</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Drug Delivery Systems</term>
<term>Drug Stability</term>
<term>Female</term>
<term>Indicators and Reagents</term>
<term>Indium Radioisotopes</term>
<term>Iodine Radioisotopes</term>
<term>Isotope Labeling</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Radioimmunotherapy</term>
<term>Tissue Distribution</term>
</keywords>
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<front><div type="abstract" xml:lang="en">The aim of this study was to design liposomes as radioactivity carriers for pretargeted radioimmunotherapy with favorable pharmacokinetic parameters. To monitor the liposomes integrity in vivo, their surface was radiolabeled with indium-111 bound to DTPA-derivatized phosphatidylethanolamine (DSPE-DTPA) and the aqueous phase was labeled by using an original active loading technique of radioiodinated Bolton-Hunter reagent (BH) that reacts with pre-encapsulated arginine to form a positively charged conjugate ((125)I-BH-arginine). Different formulations of doubly radiolabeled liposomes were tested in vitro and in vivo to evaluate radiolabeling stability, integrity of the vesicles and their pharmacokinetics. Radiolabeling yields were high (surface >75%, encapsulation >60%) and stable (>85% after 24 h in serum 37 degrees C). In vivo, the pharmacokinetic behavior of doubly radiolabeled liposomes was strongly dependant on the formulation. Blood clearance of PEGylated liposomes (DSPC/Chol/DSPE-DTPA/DSPE-PEG5%) was 0.15 mL/h compared to a conventional formulation (DSPC/Chol/DSPE-DTPA: clearance 1.44 mL/h). Non-encapsulated BH-arginine conjugate was quickly eliminated in urine (clearance 6.04 mL/h). Blood kinetics of the two radionuclides were similar and radiochromatographic profiles of mice serum confirmed the integrity of circulating liposomes. The significant reduction of activity uptake in organs after liposome catabolism (liver and spleen), achieved by the rapid renal elimination of (125)I-BH-arginine, should bring significant improvements for targeted radionuclide therapy with sterically-stabilized liposomes.</div>
</front>
</TEI>
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<DateCreated><Year>2007</Year>
<Month>10</Month>
<Day>01</Day>
</DateCreated>
<DateCompleted><Year>2008</Year>
<Month>01</Month>
<Day>16</Day>
</DateCompleted>
<DateRevised><Year>2013</Year>
<Month>11</Month>
<Day>21</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">0378-5173</ISSN>
<JournalIssue CitedMedium="Print"><Volume>344</Volume>
<Issue>1-2</Issue>
<PubDate><Year>2007</Year>
<Month>Nov</Month>
<Day>1</Day>
</PubDate>
</JournalIssue>
<Title>International journal of pharmaceutics</Title>
<ISOAbbreviation>Int J Pharm</ISOAbbreviation>
</Journal>
<ArticleTitle>Doubly radiolabeled liposomes for pretargeted radioimmunotherapy.</ArticleTitle>
<Pagination><MedlinePgn>110-7</MedlinePgn>
</Pagination>
<Abstract><AbstractText>The aim of this study was to design liposomes as radioactivity carriers for pretargeted radioimmunotherapy with favorable pharmacokinetic parameters. To monitor the liposomes integrity in vivo, their surface was radiolabeled with indium-111 bound to DTPA-derivatized phosphatidylethanolamine (DSPE-DTPA) and the aqueous phase was labeled by using an original active loading technique of radioiodinated Bolton-Hunter reagent (BH) that reacts with pre-encapsulated arginine to form a positively charged conjugate ((125)I-BH-arginine). Different formulations of doubly radiolabeled liposomes were tested in vitro and in vivo to evaluate radiolabeling stability, integrity of the vesicles and their pharmacokinetics. Radiolabeling yields were high (surface >75%, encapsulation >60%) and stable (>85% after 24 h in serum 37 degrees C). In vivo, the pharmacokinetic behavior of doubly radiolabeled liposomes was strongly dependant on the formulation. Blood clearance of PEGylated liposomes (DSPC/Chol/DSPE-DTPA/DSPE-PEG5%) was 0.15 mL/h compared to a conventional formulation (DSPC/Chol/DSPE-DTPA: clearance 1.44 mL/h). Non-encapsulated BH-arginine conjugate was quickly eliminated in urine (clearance 6.04 mL/h). Blood kinetics of the two radionuclides were similar and radiochromatographic profiles of mice serum confirmed the integrity of circulating liposomes. The significant reduction of activity uptake in organs after liposome catabolism (liver and spleen), achieved by the rapid renal elimination of (125)I-BH-arginine, should bring significant improvements for targeted radionuclide therapy with sterically-stabilized liposomes.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Mougin-Degraef</LastName>
<ForeName>M</ForeName>
<Initials>M</Initials>
<Affiliation>Département de recherche en cancérologie, INSERM, U601, Université de Nantes, 9 quai Moncousu 44093, Nantes Cedex 1, France. marie.mougin@nantes.inserm.fr</Affiliation>
</Author>
<Author ValidYN="Y"><LastName>Bourdeau</LastName>
<ForeName>C</ForeName>
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<Author ValidYN="Y"><LastName>Jestin</LastName>
<ForeName>E</ForeName>
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<Author ValidYN="Y"><LastName>Saï-Maurel</LastName>
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<Author ValidYN="Y"><LastName>Faivre-Chauvet</LastName>
<ForeName>A</ForeName>
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<Language>eng</Language>
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<ArticleDate DateType="Electronic"><Year>2007</Year>
<Month>05</Month>
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<MedlineJournalInfo><Country>Netherlands</Country>
<MedlineTA>Int J Pharm</MedlineTA>
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<ISSNLinking>0378-5173</ISSNLinking>
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