Remote loading of liposomes with a 124 I-radioiodinated compound and their in vivo evaluation by PET/CT in a murine tumor model.

Autor: Engudar G; Department of Chemistry, Technical University of Denmark, 2800 Lyngby, Denmark.; Center for Nanomedicine and Theranostics, Denmark., Schaarup-Jensen H; Department of Chemistry, Technical University of Denmark, 2800 Lyngby, Denmark.; Center for Nanomedicine and Theranostics, Denmark., Fliedner FP; Cluster for Molecular Imaging, Dept. of Biomedical Sciences and Dept. of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet and University of Copenhagen, 2200 Copenhagen., Hansen AE; Cluster for Molecular Imaging, Dept. of Biomedical Sciences and Dept. of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet and University of Copenhagen, 2200 Copenhagen.; Department of Micro- and Nanotechnology, Technical University of Denmark, 2800 Lyngby, Denmark.; Center for Nanomedicine and Theranostics, Denmark., Kempen P; Department of Micro- and Nanotechnology, Technical University of Denmark, 2800 Lyngby, Denmark.; Center for Nanomedicine and Theranostics, Denmark., Jølck RI; Department of Micro- and Nanotechnology, Technical University of Denmark, 2800 Lyngby, Denmark.; Center for Nanomedicine and Theranostics, Denmark., Kjæer A; Cluster for Molecular Imaging, Dept. of Biomedical Sciences and Dept. of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet and University of Copenhagen, 2200 Copenhagen., Andresen TL; Department of Micro- and Nanotechnology, Technical University of Denmark, 2800 Lyngby, Denmark.; Center for Nanomedicine and Theranostics, Denmark., Clausen MH; Department of Chemistry, Technical University of Denmark, 2800 Lyngby, Denmark.; Center for Nanomedicine and Theranostics, Denmark., Jensen AI; Center for Nuclear Technologies, Technical University of Denmark, 4000 Roskilde, Denmark.; Center for Nanomedicine and Theranostics, Denmark., Henriksen JR; Department of Micro- and Nanotechnology, Technical University of Denmark, 2800 Lyngby, Denmark.; Center for Nanomedicine and Theranostics, Denmark.
Jazyk: angličtina
Zdroj: Theranostics [Theranostics] 2018 Nov 12; Vol. 8 (21), pp. 5828-5841. Date of Electronic Publication: 2018 Nov 12 (Print Publication: 2018).
DOI: 10.7150/thno.26706
Abstrakt: Long circulating liposomes entrapping iodinated and radioiodinated compounds offer a highly versatile theranostic platform. Here we report a new methodology for efficient and high-yield loading of such compounds into liposomes, enabling CT/SPECT/PET imaging and 131 I-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 124 I (t 1/2 = 4.18 days) for PET or 125 I (t 1/2 = 59.5 days) for SPECT, through an aromatic Finkelstein reaction. Results: Quantitative loading efficiencies (>99%) were achieved at optimized conditions. The 124 I-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.
Competing Interests: Competing Interests: The authors have declared that no competing interest exists.
Databáze: MEDLINE
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