Contrast enhanced MRI-guided photodynamic therapy for site-specific cancer treatment.

Photodynamic therapy (PDT) is a minimally invasive and effective approach for cancer treatment. It is potentially useful for treating tumors that are not accessible to surgery, radiation, or destructive ablations, and are resistant to chemotherapy. Efficacious treatment of interstitial tumors with PDT requires efficient delivery of photosensitizers and accurate location of tumor tissues for effective light irradiations. In this study we performed contrast-enhanced (CE) MRI-guided PDT with a bifunctional polymer conjugate containing both a magnetic resonance imaging (MRI) contrast agent and a photosensitizer, poly(L-glutamic acid) (PGA)-(Gd-DO3A)-mesochlorin e(6) (Mce(6)). The efficacy of the bifunctional conjugate in cancer CE-MRI and cancer treatment was evaluated in athymic nude mice bearing MDA-MB-231 human breast carcinoma xenografts, with PGA-(Gd-DO3A) used as a control. The polymer conjugates preferentially accumulated in the solid tumor due to the hyperpermeability of the tumor vasculature, resulting in significant tumor enhancement for accurate tumor detection and localization by MRI. Significant therapeutic response was observed for PDT with the bifunctional conjugate as compared to the control. CE-MRI-guided PDT with the bifunctional conjugate is effective for tumor detection and minimally invasive cancer treatment.

Pharmacokinetics and tissue retention of (Gd-DTPA)-cystamine copolymers, a biodegradable macromolecular magnetic resonance imaging contrast agent.

PURPOSE: To investigate the pharmacokinetics, long-term tissue retention of Gd(III) ions, and magnetic resonance imaging (MRI) contrast enhancement of extracellular biodegradable macromolecular Gd(III) complexes, (Gd-DTPA)-cystamine copolymers (GDCC), of different molecular weights. METHODS: The pharmacokinetics of blood clearance and long-term Gd(III) retention of GDCC were investigated in Sprague-Dawley rats. Pharmacokinetic parameters were calculated by using a two-compartment model. The blood pool contrast enhancement of GDCC was evaluated in Sprague-Dawley rats on a Siemens Trio 3T MR scanner. Gd-(DTPA-BMA) was used as a control. RESULTS: The alpha phase half-life of Gd-(DTPA-BMA) and GDCC with molecular weights of 18,000 (GDCC-18) and 60,000 Da (GDCC-60) was 0.48 +/- 0.16 min, 1.08 +/- 0.24 min, and 1.74 +/- 0.57 min, and the beta phase half-life was 21.2 +/- 5.5 min, 26.5 +/- 5.9 min, and 53.7 +/- 15.9 min, respectively. GDCC had minimal long-term Gd tissue retention comparable to that of Gd-(DTPA-BMA). GDCC resulted in more significant contrast enhancement in the blood pool than Gd-(DTPA-BMA). CONCLUSIONS: GDCC provides a prolonged blood pool retention time for effective MRI contrast enhancement and then clears rapidly with minimal accumulation of Gd (III) ions. It is promising for further development as a blood pool MRI contrast agent.