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Comparison of three remote radiolabelling methods for long-circulating liposomes.
- Source :
-
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2015 Dec 28; Vol. 220 (Pt A), pp. 239-244. Date of Electronic Publication: 2015 Oct 26. - Publication Year :
- 2015
-
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.
- Subjects :
- Animals
Contrast Media administration & dosage
Contrast Media chemistry
Disease Models, Animal
Female
Humans
Indium administration & dosage
Indium blood
Indium chemistry
Isotope Labeling
Liposomes
Muscle, Skeletal metabolism
Pentetic Acid administration & dosage
Pentetic Acid blood
Pentetic Acid chemistry
Phosphatidylethanolamines administration & dosage
Phosphatidylethanolamines blood
Phosphatidylethanolamines chemistry
Staphylococcal Infections metabolism
Tissue Distribution
Tomography, Emission-Computed, Single-Photon
X-Ray Microtomography
Contrast Media pharmacokinetics
Indium pharmacokinetics
Indium Radioisotopes
Muscle, Skeletal diagnostic imaging
Pentetic Acid pharmacokinetics
Phosphatidylethanolamines pharmacokinetics
Staphylococcal Infections diagnostic imaging
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4995
- Volume :
- 220
- Issue :
- Pt A
- Database :
- MEDLINE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Publication Type :
- Academic Journal
- Accession number :
- 26514291
- Full Text :
- https://doi.org/10.1016/j.jconrel.2015.10.043