Poly(iohexol) nanoparticles as contrast agents for in vivo X-ray computed tomography imaging

Abstract

Biocompatible poly(iohexol) nanoparticles, prepared through cross-linking of iohexol and hexamethylene diisocyanate followed by coprecipitation of the resulting cross-linked polymer with mPEG-polylactide, were utilized as contrast agents for in vivo X-ray computed tomography (CT) imaging. Compared to conventional small-molecule contrast agents, poly(iohexol) nanoparticles exhibited substantially protracted retention within the tumor bed and a 36-fold increase in CT contrast 4 h post injection, which makes it possible to acquire CT images with improved diagnosis accuracy over a broad time frame without multiple administrations.

Figure 1

(A) Synthetic illustration of cross-linked poly(iohexol) and formulation of PEGylated poly(iohexol) NPs. (B) Dynamic light scattering (DLS) analysis of NPs in water (0.5 mg/mL) and SEM image of NPs. (C) Stability of NPs following dilution with PBS (1×) or human serum (HS) buffer (HS/PBS = 1/1, v/v) for one fold and further incubation at RT for different time.

Figure 2

(A) Serial axial CT images of the MCF-7 tumors in mice following intratumoral injection of 200 μL of iohexol (upper panel) and poly(iohexol) NPs (lower panel) at 50 mg iohexol/kg. Images were taken before injection, and 5 min, 1 h and 4 h post injection. Arrows indicate the enhanced contrast regions in the tumor bed. (B) Serial sections of coronal CT images in MCF-7 xenografts bearing mice following the same treatment as described in (A). Arrows indicate the enhanced contrast regions in the bladder. (C) Enhanced density (ΔHU, HU = Hounsfield unit) of tumors 5 min, 1 h and 4 h after injection of poly(iohexol) NPs or iohexol.

Figure 3

(A) Serial fluoroscopic images of C57BL/6 mice following jugular vein injection of 200 μL of conventional iodinated contrast agent (iohexol) solution (upper panel) and poly(iohexol) NP solution (lower panel) at 250 mg iohexol/kg, respectively. Images taken at 0 min and 60 min after injection were shown. Arrows indicated the enhanced contrast in the bladder regions. (B) In vivo circulation time of poly(iohexol) NP and iohexol. ⁶⁴Cu labeled poly(iohexol) NP and iohexol were injected intravenously through the tail vein of mice. At various time points (5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, and 48 h), blood was withdrawn intraorbitally and the radioactivity was measured by the γ-counter to evaluate the systemic circulation of the poly(iohexol) NP (red) and iohexol (blue) (n=3).