SPECT/CT imaging of radiolabeled cubosomes and hexosomes for potential theranostic applications.
We have developed a highly efficient method for the radiolabeling of phytantriol (PHYT)/oleic acid (OA)-based hexosomes based on the surface chelation of technetium-99m ((99m)Tc) to preformed hexosomes using the polyamine 1, 12-diamino-3, 6, 9-triazododecane (SpmTrien) as chelating agent. We also report on the unsuccessful labeling of cubosomes using the well-known chelating agent hexamethylpropyleneamine oxime (HMPAO). The (99m)Tc-labeled SpmTrien-hexosomes ((99m)Tc-SpmTrien-hexosomes) were synthesized with good radiolabeling (84%) and high radiochemical purity (>90%). The effect of radiolabeling on the internal nanostructure and the overall size of these aqueous dispersions was investigated by using synchrotron small angle X-ray scattering (SAXS), dynamic light scattering (DLS), and transmission electron cryo microscopy (cryo-TEM). Further, we show the utility of (99m)Tc-SpmTrien-hexosomes for the in vivo imaging of healthy mice using single photon emission computed tomography (SPECT) in combination with computed tomography (CT), i.e. SPECT/CT. SPECT/CT experiments of subcutaneously administered (99m)Tc-SpmTrien-hexosomes to the flank of mice showed a high stability in vivo allowing imaging of the distribution of the radiolabeled hexosomes for up to 24 h. These injected (99m)Tc-SpmTrien-hexosomes formed a deposit within the subcutaneous adipose tissue, displaying a high biodistribution of ≈ 343% injected dose/g tissue (%ID/g), with negligible uptake in other organs and tissues. The developed (99m)Tc labeling method for PHYT/OA-based hexosomes could further serve as a useful tool for investigating and imaging the in vivo performance of cubosomal and hexosomal drug nanocarriers.
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Christa
C
Nilsson
Brianda
B
Barrios-Lopez
Annukka
A
Kallinen
Pasi
P
Laurinmäki
Sarah J
SJ
Butcher
Mari
M
Raki
Janne
J
Weisell
Kim
K
Bergström
Susan Weng
SW
Larsen
Jesper
J
Østergaard
Claus
C
Larsen
Arto
A
Urtti
Anu J
AJ
Airaksinen
Anan
A
Yaghmur
D000818:Animals; D002614:Chelating Agents / Q000737:chemistry; D051379:Mice; D013667:Technetium; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D002614:Chelating Agents; D013667:Technetium
Cubosomes; Hexosomes; In vivo; Radiolabeling methods; SPECT/CT-imaging; Theranostics