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 (fPV), endothelium transfer coefficient (KPS), 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 fPV, KPS, 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. © 2009 Wiley-Liss, Inc.