Application of a biodegradable macromolecular contrast agent in dynamic contrast-enhanced MRI for assessing the efficacy of indocyanine green-enhanced photothermal cancer therapy

Abstract

Purpose: To investigate the effectiveness of a polydisulfide-based biodegradable macromolecular contrast agent, (Gd-DTPA)-cystamine copolymers (GDCC), in assessing the efficacy of indocyanine green-enhanced photothermal cancer therapy using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

Materials and methods: Breast cancer xenografts in mice were injected with indocyanine green and irradiated with a laser. The efficacy was assessed using DCE-MRI with GDCC of 40 kDa (GDCC-40) at 4 hours and 7 days after the treatment. The uptake of GDCC-40 by the tumors was fit to a two-compartment model to obtain tumor vascular parameters, including fractional plasma volume (f(PV)), endothelium transfer coefficient (K(PS)), and permeability surface area product (PS).

Results: GDCC-40 resulted in similar tumor vascular parameters at three doses, with larger standard deviations at lower doses. The values of f(PV), K(PS), and PS of the treated tumors were smaller (P < 0.05) than those of untreated tumors at 4 hours after the treatment and recovered to pretreatment values (P > 0.05) at 7 days after the treatment.

Conclusion: DCE-MRI with GDCC-40 is effective for assessing tumor early response to dye-enhanced photothermal therapy and detecting tumor relapse after the treatment. GDCC-40 has a potential to noninvasively monitor anticancer therapies with DCE-MRI.

Figure 1

Representative T1-weighted 2D spin-echo magnetic resonance images of axial slice of a mouse bearing 2 bilateral tumors: the control tumor (thin arrow) and treated tumor (thick arrow, 4 hr after treatment) before (a) and 15 minutes (b) after the injection GDCC-40 at a dose of 0.05 mmol-Gd/kg. The direction of the thick arrow is the same as the laser path.

Figure 2

Representative signal intensity time curves of tumor rim and muscle enhanced by GDCC-40 at a dose of 0.05 mmol-Gd/kg.

Figure 3

Representative f^PV map (a and b) and K^PS map (c and d, in ml/min/100 cc) of control (left tumor in the images, pointed by thin arrows) and treated tumors (right tumor in the images, pointed by thick arrows, which also show the laser path) constructed from the DCE-MRI data with GDCC-40 at 4 hours (a and c) and 7 days after treatment (b and d). The images are axial imaging slices of a mouse.