title: Comparison of three remote radiolabelling methods for long-circulating liposomes.
abstract: Long-circulating liposomes (LCL) are often used as a drug carrier system to improve the therapeutic index of water-soluble drugs. To track these LCL in vivo, they can be radiolabelled with (111)In-oxine. For this labelling method, generally DTPA is encapsulated in the aqueous phase of LCL (DTPA-LCL). Alternatively, LCL can be labelled with (111)InCl3 after incorporation of DTPA-conjugated DSPE in the lipid bilayer (DTPA-DSPE LCL). Here, we compared the in vitro properties of DTPA-DSPE LCL with those of DTPA LCL and empty LCL. Additionally, we compared the in vivo performance of DTPA-DSPE LCL with those of DTPA LCL in mice. DTPA LCL (88 nm) and empty LCL (84 nm) were labelled with (111)In-oxine, and DTPA-DSPE LCL (83 nm) were labelled with (111)InCl3. Labelling efficiency at increasing specific activity was determined. In vitro stability of (111)In-labelled LCL was determined in human serum at 37 °C. The in vivo properties of (111)In-labelled LCL were determined in mice with a Staphylococcus aureus infection in the thigh muscle. Image acquisition, blood sampling and biodistribution studies were performed 1, 4 (blood sampling only), 24, 48 and 72 h p.i. of (111)In-labelled LCL. DTPA-DSPE LCL could be labelled efficiently at a much higher specific activity compared to DTPA LCL and empty LCL: > 90% at 15 GBq/mmol, > 90% at 150 MBq/mmol and 60–65% at 150 MBq/mmol, respectively. (111)In-labelled DTPA-DSPE LCL and DTPA LCL were stable in human serum, regarding label retention, for at least 48 h at 37 °C (> 98% retention of the radiolabel). In contrast, only 68% radiolabel was retained in empty LCL after 48 h. In vivo targeting of (111)In-DTPA-DSPE LCL to the abscess was comparable to targeting of (111)In-DTPA LCL (3.5 ± 0.9%ID/g and 3.4 ± 0.9%ID/g abscess uptake respectively, 48 h p.i.). In conclusion, labelling of DTPA-DSPE LCL with (111)InCl3 represents a robust, easy and fast procedure which is preferred over the more laborious conventional labelling of DTPA-LCL with (111)In-oxine.
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Tessa.vanderGeest@radboudumc.nl.
authors.forename: Tessa
authors.initials: T
authors.lastname: van der Geest
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Laverman
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Danny
authors.initials: D
authors.lastname: Gerrits
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Gerben M
authors.initials: GM
authors.lastname: Franssen
authors.affiliation: Department of Targeted Therapeutics, MIRA Institute, University of Twente, Enschede, The Netherlands; Department of Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH-Aachen University, Aachen, Germany.
authors.forename: Josbert M
authors.initials: JM
authors.lastname: Metselaar
authors.affiliation: Department of Targeted Therapeutics, MIRA Institute, University of Twente, Enschede, The Netherlands; Department of Pharmaceutics, Utrecht Institute for Parmaceutial Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007204:Indium / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D007205:Indium Radioisotopes; D007553:Isotope Labeling; D008081:Liposomes; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging* / Q000378:metabolism; D004369:Pentetic Acid / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D013203:Staphylococcal Infections / Q000000981:diagnostic imaging* / Q000378:metabolism; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D055114:X-Ray Microtomography
chemical_list: D003287:Contrast Media; D007205:Indium Radioisotopes; D008081:Liposomes; D010714:Phosphatidylethanolamines; D007204:Indium; C038089:1,2-distearoylphosphatidylethanolamine; C020758:indium trichloride; D004369:Pentetic Acid
keywords: 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (PubChem CID 406952); 2-[bis[2-bis(carboxymethyl)amino]ethyl]amino] acetic acid (PubChem CID: 3053), Indium Oxinate (PubChem CID: 3034762); Cholesterol (PubChem CID: 5997); DTPA-DSPE-PEG liposomes; DTPA-PEG liposomes; Dipalmitoylphosphatidylcholine (PubChem CID: 452110); MicroSPECT/CT imaging; Staphylococcus aureus; Targeting