In vitro assessment of poly-iodinated triglyceride reconstituted low-density lipoprotein: initial steps toward CT molecular imaging.
OBJECTIVE
Targeted molecular probes offer the potential for greater specificity in cancer imaging with contrast-enhanced computed tomography (CT). We investigate a low-density lipoprotein (LDL) nanoparticle loaded with poly-iodinated triglyceride (ITG) in a proof of concept study of targeted x-ray imaging. LDLs are targeted to the LDL cell surface receptor (LDLR), which is overexpressed in several tumor types. The LDL-LDLR pathway presents a high-capacity and self-renewing transport system for molecular imaging in CT.


METHODS
ITG was synthesized and loaded into the core of LDL particles to form a reconstituted nanoparticle, hereafter referred to as (rITG)LDL. Particle size was measured by dynamic light scattering. The x-ray attenuation of the (rITG)LDL solution was measured with CT imaging and signal enhancement was calibrated for equivalent iodine concentration. Cultured human hepatoblastoma G2 (HepG2) cells, which overexpress LDLR, were incubated with (rITG)LDL with or without native LDL. The cells were imaged with CT to characterize particle sequestration.


RESULTS
Reconstitution of LDL with ITG was successful and did not compromise the targeting function of the particle. Measurement of the x-ray attenuation properties of the (rITG)LDL solution revealed an effective iodine concentration of 0.78 mg/mL. In vitro studies of HepG2 cells demonstrated a significant increase in CT image intensity over control cells when incubated with (rITG)LDL.


CONCLUSIONS
The in vitro results of this study suggest that (rITG)LDL can provide adequate image enhancement for CT molecular imaging. Potential applications include breast imaging and small animal imaging at low x-ray energies. In vivo experiments will be required to verify that tumor uptake of (rITG)LDL is sufficient for enhanced detection. Use at higher x-ray energies, as used in conventional CT, will require a further increase in iodine loading.
Hill
Melissa L
ML
Imaging Research, Sunnybrook Health Sciences Centre, Room S6-57, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.
Corbin
Ian R
IR
Levitin
Ronald B
RB
Cao
Weiguo
W
Mainprize
James G
JG
Yaffe
Martin J
MJ
Zheng
Gang
G
D045744:Cell Line, Tumor; D003287:Contrast Media / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D018197:Hepatoblastoma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000493:pharmacokinetics*; D057054:Molecular Imaging / Q000379:methods*; D011973:Receptors, LDL / Q000378:metabolism*; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed / Q000379:methods*
D003287:Contrast Media; D008077:Lipoproteins, LDL; D011973:Receptors, LDL