186Re-liposome labeling using 186Re-SNS/S complexes: In vitro stability, imaging, and biodistribution in rats

Ande Bao, Beth Goins, Robert Klipper, George Negrete, William T Phillips

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Liposomes are important carriers for controlling the spatial and temporal distribution of drug molecules or other bioactive molecules. Radiolabeled liposomes have potential applications in diagnostic imaging and radionuclide therapy. The purpose of this study was to develop a practical method for labeling liposomes with therapeutic rhenium radionuclides, using 186Re as an example. Methods: An SNS pattern ligand, N,N-bis(2-mercaptoethyl)-N′,N′-diethylethylenediamine (BMEDA), and an S pattern ligand, benzene thiol (BT), were used to make 2 kinds of 186Re-SNS/S complexes, 186Re-BMEDA and 186Re-BMEDA + BT. These 186Re-SNS/S complexes were mixed with neutral liposomes encapsulating cysteine or (NH4) 2SO4 to prepare 186Re-liposomes. The in vitro labeling stability of 186Re-liposomes was investigated by incubation in 50% fetal bovine serum/50% phosphate-buffered saline, pH 7.4, at 37°C. Rat distribution studies of 186Re-liposomes after intravenous injection were also performed. Results: The labeling efficiencies of 186Re-liposomes were 52.9%-81.3% depending on the 186Re-SNS/S complex chosen and whether cysteine- or (NH 4)2SO4-encapsulated liposomes were used. 186Re-(NH4)2SO4 liposomes labeled with 186Re-BMEDA had the best in vitro labeling stability in serum with 89.8% ± 3.1% of the radioactivity associated with liposomes at 24 h and 76.2% ± 5.1% at 96 h. A specific activity of 1.85 GBq (50 mCi) of 186Re per 50 mg of phospholipid could be achieved with good labeling stability. Biodistributions were followed for 72 h and showed good in vivo stability for 186Re-liposomes that was characterized by a slow blood clearance and a gradually increasing spleen accumulation. 186Re-BMEDA alone had fast blood clearance and no accumulation in spleen. Conclusion: A practical method for labeling liposomes with 186Re using 186Re-SNS/S complexes is described. The labeled 186Re- liposomes were stable in serum and in vivo and could potentially be useful for radionuclide therapy.

Original languageEnglish (US)
Pages (from-to)1992-1999
Number of pages8
JournalJournal of Nuclear Medicine
Volume44
Issue number12
StatePublished - Dec 2003

Fingerprint

Liposomes
Radioisotopes
In Vitro Techniques
Benzene
Sulfhydryl Compounds
Cysteine
Spleen
Serum
Rhenium
Ligands
Diagnostic Imaging
Intravenous Injections
Radioactivity
Phospholipids
Therapeutics
Phosphates

Keywords

  • Re
  • Biodistribution
  • Liposomes
  • Radiolabeling
  • Radionuclide therapy
  • SNS/S complexes

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Bao, A., Goins, B., Klipper, R., Negrete, G., & Phillips, W. T. (2003). 186Re-liposome labeling using 186Re-SNS/S complexes: In vitro stability, imaging, and biodistribution in rats. Journal of Nuclear Medicine, 44(12), 1992-1999.

186Re-liposome labeling using 186Re-SNS/S complexes : In vitro stability, imaging, and biodistribution in rats. / Bao, Ande; Goins, Beth; Klipper, Robert; Negrete, George; Phillips, William T.

In: Journal of Nuclear Medicine, Vol. 44, No. 12, 12.2003, p. 1992-1999.

Research output: Contribution to journalArticle

Bao, A, Goins, B, Klipper, R, Negrete, G & Phillips, WT 2003, '186Re-liposome labeling using 186Re-SNS/S complexes: In vitro stability, imaging, and biodistribution in rats', Journal of Nuclear Medicine, vol. 44, no. 12, pp. 1992-1999.
Bao, Ande ; Goins, Beth ; Klipper, Robert ; Negrete, George ; Phillips, William T. / 186Re-liposome labeling using 186Re-SNS/S complexes : In vitro stability, imaging, and biodistribution in rats. In: Journal of Nuclear Medicine. 2003 ; Vol. 44, No. 12. pp. 1992-1999.
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title = "186Re-liposome labeling using 186Re-SNS/S complexes: In vitro stability, imaging, and biodistribution in rats",
abstract = "Liposomes are important carriers for controlling the spatial and temporal distribution of drug molecules or other bioactive molecules. Radiolabeled liposomes have potential applications in diagnostic imaging and radionuclide therapy. The purpose of this study was to develop a practical method for labeling liposomes with therapeutic rhenium radionuclides, using 186Re as an example. Methods: An SNS pattern ligand, N,N-bis(2-mercaptoethyl)-N′,N′-diethylethylenediamine (BMEDA), and an S pattern ligand, benzene thiol (BT), were used to make 2 kinds of 186Re-SNS/S complexes, 186Re-BMEDA and 186Re-BMEDA + BT. These 186Re-SNS/S complexes were mixed with neutral liposomes encapsulating cysteine or (NH4) 2SO4 to prepare 186Re-liposomes. The in vitro labeling stability of 186Re-liposomes was investigated by incubation in 50{\%} fetal bovine serum/50{\%} phosphate-buffered saline, pH 7.4, at 37°C. Rat distribution studies of 186Re-liposomes after intravenous injection were also performed. Results: The labeling efficiencies of 186Re-liposomes were 52.9{\%}-81.3{\%} depending on the 186Re-SNS/S complex chosen and whether cysteine- or (NH 4)2SO4-encapsulated liposomes were used. 186Re-(NH4)2SO4 liposomes labeled with 186Re-BMEDA had the best in vitro labeling stability in serum with 89.8{\%} ± 3.1{\%} of the radioactivity associated with liposomes at 24 h and 76.2{\%} ± 5.1{\%} at 96 h. A specific activity of 1.85 GBq (50 mCi) of 186Re per 50 mg of phospholipid could be achieved with good labeling stability. Biodistributions were followed for 72 h and showed good in vivo stability for 186Re-liposomes that was characterized by a slow blood clearance and a gradually increasing spleen accumulation. 186Re-BMEDA alone had fast blood clearance and no accumulation in spleen. Conclusion: A practical method for labeling liposomes with 186Re using 186Re-SNS/S complexes is described. The labeled 186Re- liposomes were stable in serum and in vivo and could potentially be useful for radionuclide therapy.",
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AU - Negrete, George

AU - Phillips, William T

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N2 - Liposomes are important carriers for controlling the spatial and temporal distribution of drug molecules or other bioactive molecules. Radiolabeled liposomes have potential applications in diagnostic imaging and radionuclide therapy. The purpose of this study was to develop a practical method for labeling liposomes with therapeutic rhenium radionuclides, using 186Re as an example. Methods: An SNS pattern ligand, N,N-bis(2-mercaptoethyl)-N′,N′-diethylethylenediamine (BMEDA), and an S pattern ligand, benzene thiol (BT), were used to make 2 kinds of 186Re-SNS/S complexes, 186Re-BMEDA and 186Re-BMEDA + BT. These 186Re-SNS/S complexes were mixed with neutral liposomes encapsulating cysteine or (NH4) 2SO4 to prepare 186Re-liposomes. The in vitro labeling stability of 186Re-liposomes was investigated by incubation in 50% fetal bovine serum/50% phosphate-buffered saline, pH 7.4, at 37°C. Rat distribution studies of 186Re-liposomes after intravenous injection were also performed. Results: The labeling efficiencies of 186Re-liposomes were 52.9%-81.3% depending on the 186Re-SNS/S complex chosen and whether cysteine- or (NH 4)2SO4-encapsulated liposomes were used. 186Re-(NH4)2SO4 liposomes labeled with 186Re-BMEDA had the best in vitro labeling stability in serum with 89.8% ± 3.1% of the radioactivity associated with liposomes at 24 h and 76.2% ± 5.1% at 96 h. A specific activity of 1.85 GBq (50 mCi) of 186Re per 50 mg of phospholipid could be achieved with good labeling stability. Biodistributions were followed for 72 h and showed good in vivo stability for 186Re-liposomes that was characterized by a slow blood clearance and a gradually increasing spleen accumulation. 186Re-BMEDA alone had fast blood clearance and no accumulation in spleen. Conclusion: A practical method for labeling liposomes with 186Re using 186Re-SNS/S complexes is described. The labeled 186Re- liposomes were stable in serum and in vivo and could potentially be useful for radionuclide therapy.

AB - Liposomes are important carriers for controlling the spatial and temporal distribution of drug molecules or other bioactive molecules. Radiolabeled liposomes have potential applications in diagnostic imaging and radionuclide therapy. The purpose of this study was to develop a practical method for labeling liposomes with therapeutic rhenium radionuclides, using 186Re as an example. Methods: An SNS pattern ligand, N,N-bis(2-mercaptoethyl)-N′,N′-diethylethylenediamine (BMEDA), and an S pattern ligand, benzene thiol (BT), were used to make 2 kinds of 186Re-SNS/S complexes, 186Re-BMEDA and 186Re-BMEDA + BT. These 186Re-SNS/S complexes were mixed with neutral liposomes encapsulating cysteine or (NH4) 2SO4 to prepare 186Re-liposomes. The in vitro labeling stability of 186Re-liposomes was investigated by incubation in 50% fetal bovine serum/50% phosphate-buffered saline, pH 7.4, at 37°C. Rat distribution studies of 186Re-liposomes after intravenous injection were also performed. Results: The labeling efficiencies of 186Re-liposomes were 52.9%-81.3% depending on the 186Re-SNS/S complex chosen and whether cysteine- or (NH 4)2SO4-encapsulated liposomes were used. 186Re-(NH4)2SO4 liposomes labeled with 186Re-BMEDA had the best in vitro labeling stability in serum with 89.8% ± 3.1% of the radioactivity associated with liposomes at 24 h and 76.2% ± 5.1% at 96 h. A specific activity of 1.85 GBq (50 mCi) of 186Re per 50 mg of phospholipid could be achieved with good labeling stability. Biodistributions were followed for 72 h and showed good in vivo stability for 186Re-liposomes that was characterized by a slow blood clearance and a gradually increasing spleen accumulation. 186Re-BMEDA alone had fast blood clearance and no accumulation in spleen. Conclusion: A practical method for labeling liposomes with 186Re using 186Re-SNS/S complexes is described. The labeled 186Re- liposomes were stable in serum and in vivo and could potentially be useful for radionuclide therapy.

KW - Re

KW - Biodistribution

KW - Liposomes

KW - Radiolabeling

KW - Radionuclide therapy

KW - SNS/S complexes

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