Real-time image-guided direct convective perfusion of intrinsic brainstem lesions. Technical note.

Recent preclinical studies have demonstrated that convection-enhanced delivery (CED) can be used to perfuse the brain and brainstem with therapeutic agents while simultaneously tracking their distribution using coinfusion of a surrogate magnetic resonance (MR) imaging tracer. The authors describe a technique for the successful clinical application of this drug delivery and monitoring paradigm to the brainstem. Two patients with progressive intrinsic brainstem lesions (one with Type 2 Gaucher disease and one with a diffuse pontine glioma) were treated with CED of putative therapeutic agents mixed with Gd-diethylenetriamene pentaacetic acid (DTPA). Both patients underwent frameless stereotactic placement of MR imaging-compatible outer guide-inner infusion cannulae. Using intraoperative MR imaging, accurate cannula placement was confirmed and real-time imaging during infusion clearly demonstrated progressive filling of the targeted region with the drug and Gd-DTPA infusate. Neither patient had clinical or imaging evidence of short- or long-term infusate-related toxicity. Using this technique, CED can be used to safely perfuse targeted regions of diseased brainstem with therapeutic agents. Coinfused imaging surrogate tracers can be used to monitor and control the distribution of therapeutic agents in vivo. Patients with a variety of intrinsic brainstem and other central nervous system disorders may benefit from a similar treatment paradigm.

[1]  E. Oldfield,et al.  Chronic interstitial infusion of protein to primate brain: determination of drug distribution and clearance with single-photon emission computerized tomography imaging. , 1997, Journal of neurosurgery.

[2]  Barry W Wessels,et al.  Safety and Feasibility of Convection-enhanced Delivery of Cotara for the Treatment of Malignant Glioma: Initial Experience in 51 Patients , 2005, Neurosurgery.

[3]  R. Brady,et al.  Therapy for the sphingolipidoses. , 1998, Archives of neurology.

[4]  G J Murray,et al.  Image-guided, direct convective delivery of glucocerebrosidase for neuronopathic Gaucher disease , 2007, Neurology.

[5]  R. Puri,et al.  Mutation and functional analysis of IL-13 receptors in human malignant glioma cells. , 2001, Oncology research.

[6]  D. Hargrave,et al.  Diffuse brainstem glioma in children: critical review of clinical trials. , 2006, The Lancet. Oncology.

[7]  J. Dambrosia,et al.  Replacement therapy for inherited enzyme deficiency--macrophage-targeted glucocerebrosidase for Gaucher's disease. , 1991, The New England journal of medicine.

[8]  Stephan E Maier,et al.  Pretreatment prediction of brain tumors' response to radiation therapy using high b-value diffusion-weighted MRI. , 2004, Neoplasia.

[9]  R. Puri,et al.  Preclinical studies with IL-13PE38QQR for therapy of malignant glioma. , 2000, Drug news & perspectives.

[10]  R. Brady,et al.  Replacement therapy for inherited enzyme deficiency. Use of purified glucocerebrosidase in Gaucher's disease. , 1974, The New England journal of medicine.

[11]  M. Verity,et al.  Infantile Gaucher's disease: neuropathology, acid hydrolase activities and negative staining observations. , 1977, Neuropadiatrie.

[12]  M. Berger,et al.  Comparison of intratumoral bolus injection and convection-enhanced delivery of radiolabeled antitenascin monoclonal antibodies. , 2006, Neurosurgical focus.

[13]  S. Kunwar Convection enhanced delivery of IL13-PE38QQR for treatment of recurrent malignant glioma: presentation of interim findings from ongoing phase 1 studies. , 2003, Acta neurochirurgica. Supplement.

[14]  R Langer,et al.  New methods of drug delivery. , 1990, Science.

[15]  R. Schiffmann,et al.  The efficacy of enzyme replacement therapy in patients with chronic neuronopathic Gaucher's disease. , 2001, The Journal of pediatrics.

[16]  S. Gebarski,et al.  Stereotaxic biopsy of intrinsic lesions of the brain stem. , 1986, Journal of neurosurgery.

[17]  E. Oldfield,et al.  Convective delivery of macromolecules into the naive and traumatized spinal cords of rats. , 1999, Journal of neurosurgery.

[18]  W. Pardridge,et al.  Drug Delivery to the Brain , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[19]  John A Butman,et al.  Successful and safe perfusion of the primate brainstem: in vivo magnetic resonance imaging of macromolecular distribution during infusion. , 2002, Journal of neurosurgery.

[20]  C. Patlak,et al.  Intrathecal chemotherapy: brain tissue profiles after ventriculocisternal perfusion. , 1975, The Journal of pharmacology and experimental therapeutics.

[21]  P F Morrison,et al.  Variables affecting convection-enhanced delivery to the striatum: a systematic examination of rate of infusion, cannula size, infusate concentration, and tissue-cannula sealing time. , 1999, Journal of neurosurgery.

[22]  R. Puri,et al.  IL-13 Receptor-Targeted Cytotoxin Cancer Therapy Leads to Complete Eradication of Tumors with the Aid of Phagocytic Cells in Nude Mice Model of Human Cancer1 , 2002, The Journal of Immunology.

[23]  R. Puri,et al.  Intratumor administration of interleukin 13 receptor-targeted cytotoxin induces apoptotic cell death in human malignant glioma tumor xenografts. , 2002, Molecular cancer therapeutics.

[24]  P F Morrison,et al.  Focal delivery during direct infusion to brain: role of flow rate, catheter diameter, and tissue mechanics. , 1999, American journal of physiology. Regulatory, integrative and comparative physiology.

[25]  I. Pastan,et al.  Human glioma cells overexpress receptors for interleukin 13 and are extremely sensitive to a novel chimeric protein composed of interleukin 13 and pseudomonas exotoxin. , 1995, Clinical cancer research : an official journal of the American Association for Cancer Research.

[26]  P F Morrison,et al.  Convection-enhanced delivery of macromolecules in the brain. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[27]  R. Puri,et al.  Interleukin‐13 receptor as a unique target for anti‐glioblastoma therapy , 2001, International journal of cancer.

[28]  P F Morrison,et al.  Convection-enhanced distribution of large molecules in gray matter during interstitial drug infusion. , 1995, Journal of neurosurgery.

[29]  C. Mignot,et al.  Type 2 Gaucher disease: 15 new cases and review of the literature , 2006, Brain and Development.

[30]  A. Vortmeyer,et al.  Real-time in vivo imaging of the convective distribution of a low-molecular-weight tracer. , 2005, Journal of neurosurgery.

[31]  E. Oldfield,et al.  Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors , 1997, Nature Medicine.

[32]  E. Oldfield,et al.  Direct convective delivery of macromolecules to the spinal cord. , 1998, Journal of neurosurgery.

[33]  M. Brechbiel,et al.  Real-time, Image-Guided, Convection-Enhanced Delivery of Interleukin 13 Bound to Pseudomonas Exotoxin , 2006, Clinical Cancer Research.

[34]  S. Donaldson,et al.  Advances toward an understanding of brainstem gliomas. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  P. Kaplan,et al.  Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5 years of treatment: a report from the Gaucher Registry. , 2002, The American journal of medicine.