Comparison of three remote radiolabelling methods for long-circulating liposomes

J Control Release. 2015 Dec 28;220(Pt A):239-244. doi: 10.1016/j.jconrel.2015.10.043. Epub 2015 Oct 26.


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.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Contrast Media / administration & dosage
  • Contrast Media / chemistry
  • Contrast Media / pharmacokinetics*
  • Disease Models, Animal
  • Female
  • Humans
  • Indium / administration & dosage
  • Indium / blood
  • Indium / chemistry
  • Indium / pharmacokinetics*
  • Indium Radioisotopes*
  • Isotope Labeling
  • Liposomes
  • Muscle, Skeletal / diagnostic imaging*
  • Muscle, Skeletal / metabolism
  • Pentetic Acid / administration & dosage
  • Pentetic Acid / blood
  • Pentetic Acid / chemistry
  • Pentetic Acid / pharmacokinetics*
  • Phosphatidylethanolamines / administration & dosage
  • Phosphatidylethanolamines / blood
  • Phosphatidylethanolamines / chemistry
  • Phosphatidylethanolamines / pharmacokinetics*
  • Staphylococcal Infections / diagnostic imaging*
  • Staphylococcal Infections / metabolism
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon
  • X-Ray Microtomography


  • Contrast Media
  • Indium Radioisotopes
  • Liposomes
  • Phosphatidylethanolamines
  • Indium
  • 1,2-distearoylphosphatidylethanolamine
  • indium trichloride
  • Pentetic Acid