Journal article
Remote loading of liposomes with a 124I-radioiodinated compound and their in vivo evaluation by PET/CT in a murine tumor model
Department of Chemistry, Technical University of Denmark1
Organic Chemistry, Department of Chemistry, Technical University of Denmark2
University of Copenhagen3
Department of Micro- and Nanotechnology, Technical University of Denmark4
Colloids and Biological Interfaces, Department of Micro- and Nanotechnology, Technical University of Denmark5
Technical University of Denmark6
Center for Nuclear Technologies, Technical University of Denmark7
The Hevesy Laboratory, Center for Nuclear Technologies, Technical University of Denmark8
Long circulating liposomes entrapping iodinated and radioiodinated compounds offer a highly versatile theranostic platform. Here we report a new methodology for efficient and high-yielding loading of such compounds into liposomes, enabling CT/SPECT/PET imaging and 131I-radiotherapy. Methods: The CT contrast agent diatrizoate was synthetically functionalized with a primary amine, which enabled its remote loading into PEGylated liposomes by either an ammonium sulfate or a citrate based pH transmembrane gradient.
Further, the amino-diatrizoate was radiolabeled with either 124I (t1/2 = 4.18 days) for PET or 125I (t1/2 = 59.5 days) for SPECT, through an aromatic Finkelstein reaction. Results: Quantitative loading efficiencies (>99%) were achieved at optimized conditions. The 124I-labeled compound was remote-loaded into liposomes, with an overall radiolabeling efficiency of 77 ± 1%, and imaged in vivo in a CT26 murine colon cancer tumor model by PET/CT.
A prolonged blood circulation half-life of 19.5 h was observed for the radiolabeled liposomes, whereas injections of the free compound were rapidly cleared. Lower accumulation was observed in the spleen, liver, kidney and tumor than what is usually seen for long-circulating liposomes. Conclusion: The lower accumulation was interpreted as release of the tracer from the liposomes within these organs after accumulation.
These results may guide the design of systems for controlled release of remote loadable drugs from liposomes.
| Language: | English |
|---|---|
| Publisher: | Ivyspring International Publisher |
| Year: | 2018 |
| Pages: | 5828-5841 |
| ISSN: | 18387640 |
| Types: | Journal article |
| DOI: | 10.7150/thno.26706 |
| ORCIDs: | 0000-0002-2706-5547 , Hansen, Anders E. , Kempen, Paul , Andresen, Thomas L. , Clausen, Mads H. , Jensen, Andreas Tue Ingemann and Henriksen, Jonas Rosager |
I-124 Iodinated imaging agents PET imaging Remote loading SDG 3 - Good Health and Well-being Transmembrane ammonium sulfate pH-gradient liposomes
Animals Colonic Neoplasms Contrast Media Diatrizoate Disease Models, Animal Iodine Radioisotopes Iodine-124 Liposomes Mice Positron Emission Tomography Computed Tomography Radiopharmaceuticals Radiotherapy Theranostic Nanomedicine iodinated imaging agents remote loading transmembrane ammonium sulfate
