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 e6 (Mce6). 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. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.

[1]  Robert C. G. Martin Intraoperative magnetic resonance imaging ablation of hepatic tumors. , 2005, American journal of surgery.

[2]  Chun Xing Li,et al.  Complete regression of well-established tumors using a novel water-soluble poly(L-glutamic acid)-paclitaxel conjugate. , 1998, Cancer research.

[3]  Jindrich Kopecek,et al.  Polymerizable Fab′ antibody fragments for targeting of anticancer drugs , 1999, Nature Biotechnology.

[4]  R. Gillies,et al.  The thioredoxin-1 inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) decreases vascular permeability in tumor xenografts monitored by dynamic contrast enhanced magnetic resonance imaging. , 2005, Clinical cancer research : an official journal of the American Association for Cancer Research.

[5]  T. Delaney,et al.  Photodynamic therapy of cancer. , 1988, Comprehensive therapy.

[6]  H. Maeda,et al.  Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[7]  P. Yamauchi,et al.  Topical photodynamic therapy in clinical dermatology , 2004, The British journal of dermatology.

[8]  E. Blout,et al.  High Molecular Weight Poly-α,L-glutamic Acid: Preparation and Optical Rotation Changes1 , 1958 .

[9]  Atle Bjørnerud,et al.  Experimental application of thermosensitive paramagnetic liposomes for monitoring magnetic resonance imaging guided thermal ablation , 2004, Magnetic resonance in medicine.

[10]  Hugh Calkins,et al.  Anatomic Stereotactic Catheter Ablation on Three-Dimensional Magnetic Resonance Images in Real Time , 2003, Circulation.

[11]  Zheng Huang,et al.  A Review of Progress in Clinical Photodynamic Therapy , 2005, Technology in cancer research & treatment.

[12]  Weili Lin,et al.  Principles of magnetic resonance imaging: a signal processing perspective [Book Review] , 2000 .

[13]  T. Dougherty Photodynamic therapy. , 1993, Photochemistry and photobiology.

[14]  Aditya K. Gupta,et al.  Photodynamic therapy and topical aminolevulinic acid: an overview. , 2003, American journal of clinical dermatology.

[15]  Meiyappan Solaiyappan,et al.  Reduction of vascular and permeable regions in solid tumors detected by macromolecular contrast magnetic resonance imaging after treatment with antiangiogenic agent TNP-470. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[16]  R. Weissleder,et al.  Polymeric nanoparticle preparation that eradicates tumors. , 2005, Nano letters.

[17]  T. Aida,et al.  Nanotechnology-based photodynamic therapy for neovascular disease using a supramolecular nanocarrier loaded with a dendritic photosensitizer. , 2005, Nano letters.

[18]  B. Pogue,et al.  Liposomal delivery of photosensitising agents , 2005, Expert opinion on drug delivery.

[19]  I. Tan,et al.  mTHPC‐mediated photodynamic therapy for early oral squamous cell carcinoma , 2004, International journal of cancer.

[20]  Y. Ikada,et al.  A novel surgical glue composed of gelatin and N-hydroxysuccinimide activated poly(L-glutamic acid): Part 1. Synthesis of activated poly(L-glutamic acid) and its gelation with gelatin. , 1998, Biomaterials.

[21]  A. Beeby,et al.  Intramolecular sensitisation of lanthanide(III) luminescence by acetophenone-containing ligands: the critical effect of para-substituents and solvent , 2002 .

[22]  K. McMasters,et al.  Intraoperative magnetic resonance imaging for ablation of hepatic tumors , 2006, Surgical Endoscopy And Other Interventional Techniques.

[23]  D. Parker,et al.  Contrast‐enhanced MRI with new biodegradable macromolecular Gd(III) complexes in tumor‐bearing mice , 2005, Magnetic resonance in medicine.

[24]  Raoul Kopelman,et al.  Multifunctional nanoparticle platforms for in vivo MRI enhancement and photodynamic therapy of a rat brain cancer , 2005 .

[25]  R. Jain,et al.  Microvascular permeability of normal and neoplastic tissues. , 1986, Microvascular research.

[26]  Lalit N. Goswami,et al.  Chlorophyll-a analogues conjugated with aminobenzyl-DTPA as potential bifunctional agents for magnetic resonance imaging and photodynamic therapy. , 2005, Bioconjugate chemistry.

[27]  R. Lauffer,et al.  Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications. , 1999, Chemical reviews.

[28]  R. Straight,et al.  HPMA copolymer delivery of chemotherapy and photodynamic therapy in ovarian cancer. , 2003, Advances in experimental medicine and biology.