Neurotherapeutics

, Volume 14, Issue 2, pp 358–371 | Cite as

Convection-Enhanced Delivery

Review

Abstract

Convection-enhanced delivery (CED) is a promising technique that generates a pressure gradient at the tip of an infusion catheter to deliver therapeutics directly through the interstitial spaces of the central nervous system. It addresses and offers solutions to many limitations of conventional techniques, allowing for delivery past the blood–brain barrier in a targeted and safe manner that can achieve therapeutic drug concentrations. CED is a broadly applicable technique that can be used to deliver a variety of therapeutic compounds for a diversity of diseases, including malignant gliomas, Parkinson’s disease, and Alzheimer’s disease. While a number of technological advances have been made since its development in the early 1990s, clinical trials with CED have been largely unsuccessful, and have illuminated a number of parameters that still need to be addressed for successful clinical application. This review addresses the physical principles behind CED, limitations in the technique, as well as means to overcome these limitations, clinical trials that have been performed, and future developments.

Key Words

Convection-enhanced delivery Malignant gliomas Drug delivery Technique Central nervous system Blood–brain barrier 

References

  1. 1.
    Kanu OO, Mehta A, Di C, et al. Glioblastoma multiforme: a review of therapeutic targets. Expert Opin Ther Targets 2009;13:701–718.CrossRefPubMedGoogle Scholar
  2. 2.
    Ostrom QT, Gittleman H, Farah P, et al. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006–2010. Neuro Oncol 2013;15(Suppl. 2):ii1-56.Google Scholar
  3. 3.
    Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987–996.CrossRefPubMedGoogle Scholar
  4. 4.
    Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009;10:459–466.CrossRefPubMedGoogle Scholar
  5. 5.
    Blasberg RG, Patlak C, Fenstermacher JD. Intrathecal chemotherapy: brain tissue profiles after ventriculocisternal perfusion. J Pharmacol Exp Ther 1975;195:73–83.PubMedGoogle Scholar
  6. 6.
    Chen PY, Ozawa T, Drummond DC, et al. Comparing routes of delivery for nanoliposomal irinotecan shows superior anti-tumor activity of local administration in treating intracranial glioblastoma xenografts. Neuro Oncol 2013;15:189–197.CrossRefPubMedGoogle Scholar
  7. 7.
    Langer R. New methods of drug delivery. Science 1990;249:1527–1533.CrossRefPubMedGoogle Scholar
  8. 8.
    Pardridge WM. Drug delivery to the brain. J Cereb Blood Flow Metab 1997;17:713–731.CrossRefPubMedGoogle Scholar
  9. 9.
    Lesniak MS, Brem H. Targeted therapy for brain tumours. Nat Rev Drug Discov 2004;3:499–508.CrossRefPubMedGoogle Scholar
  10. 10.
    Yun J, Rothrock RJ, Canoll P, Bruce JN. Convection-enhanced delivery for targeted delivery of antiglioma agents: the translational experience. J Drug Deliv 2013;2013:107573.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Zhou Z, Singh R, Souweidane MM. Convection-enhanced delivery in diffuse intrinsic pontine glioma. Curr Neuopharmacol 2017;15:116–128.CrossRefGoogle Scholar
  12. 12.
    Bobo RH, Laske DW, Akbasak A, Morrison PF, Dedrick RL, Oldfield EH. Convection-enhanced delivery of macromolecules in the brain. Proc Natl Acad Sci U S A 1994;91:2076–2080.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Morrison PF, Laske DW, Bobo H, Oldfield EH, Dedrick RL. High-flow microinfusion: tissue penetration and pharmacodynamics. Am J Physiol 1994;266:R292-305.PubMedGoogle Scholar
  14. 14.
    Lonser RR, Walbridge S, Garmestani K, et al. Successful and safe perfusion of the primate brainstem: in vivo magnetic resonance imaging of macromolecular distribution during infusion. J Neurosurg 2002;97:905–913.CrossRefPubMedGoogle Scholar
  15. 15.
    Nguyen TT, Pannu YS, Sung C, et al. Convective distribution of macromolecules in the primate brain demonstrated using computerized tomography and magnetic resonance imaging. J Neurosurg 2003;98:584–590.CrossRefPubMedGoogle Scholar
  16. 16.
    Raghavan R, Brady ML, Rodriguez-Ponce MI, Hartlep A, Pedain C, Sampson JH. Convection-enhanced delivery of therapeutics for brain disease, and its optimization. Neurosurg Focus 2006;20:E12.CrossRefPubMedGoogle Scholar
  17. 17.
    Corem-Salkmon E, Ram Z, Daniels D, et al. Convection-enhanced delivery of methotrexate-loaded maghemite nanoparticles. Int J Nanomedicine 2011;6:1595–1602.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Lonser RR, Sarntinoranont M, Morrison PF, Oldfield EH. Convection-enhanced delivery to the central nervous system. J Neurosurg 2015;122:697–706.CrossRefPubMedGoogle Scholar
  19. 19.
    Heiss JD, Walbridge S, Morrison P, et al. Local distribution and toxicity of prolonged hippocampal infusion of muscimol. J Neurosurg 2005;103:1035–1045.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Lieberman DM, Laske DW, Morrison PF, Bankiewicz KS, Oldfield EH. Convection-enhanced distribution of large molecules in gray matter during interstitial drug infusion. J Neurosurg 1995;82:1021–1029.CrossRefPubMedGoogle Scholar
  21. 21.
    Lonser RR, Corthesy ME, Morrison PF, Gogate N, Oldfield EH. Convection-enhanced selective excitotoxic ablation of the neurons of the globus pallidus internus for treatment of parkinsonism in nonhuman primates. J Neurosurg 1999;91:294–302.CrossRefPubMedGoogle Scholar
  22. 22.
    Ciesielska A, Mittermeyer G, Hadaczek P, Kells AP, Forsayeth J, Bankiewicz KS. Anterograde axonal transport of AAV2-GDNF in rat basal ganglia. Mol Ther 2011;19:922–927.CrossRefPubMedGoogle Scholar
  23. 23.
    Kells AP, Hadaczek P, Yin D, et al. Efficient gene therapy-based method for the delivery of therapeutics to primate cortex. Proc Natl Acad Sci U S A 2009;106:2407–2411.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Ksendzovsky A, Walbridge S, Saunders RC, Asthagiri AR, Heiss JD, Lonser RR. Convection-enhanced delivery of M13 bacteriophage to the brain. J Neurosurg 2012;117:197–203.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Barker FG, 2nd, Chang SM, Gutin PH, et al. Survival and functional status after resection of recurrent glioblastoma multiforme. Neurosurgery 1998;42:709–720.CrossRefPubMedGoogle Scholar
  26. 26.
    Lonser RR, Gogate N, Morrison PF, Wood JD, Oldfield EH. Direct convective delivery of macromolecules to the spinal cord. J Neurosurg 1998;89:616–622.CrossRefPubMedGoogle Scholar
  27. 27.
    Lonser RR, Weil RJ, Morrison PF, Governale LS, Oldfield EH. Direct convective delivery of macromolecules to peripheral nerves. J Neurosurg 1998;89:610–615.CrossRefPubMedGoogle Scholar
  28. 28.
    Murad GJ, Walbridge S, Morrison PF, et al. Image-guided convection-enhanced delivery of gemcitabine to the brainstem. J Neurosurg 2007;106:351–356.CrossRefPubMedGoogle Scholar
  29. 29.
    Asthagiri AR, Walbridge S, Heiss JD, Lonser RR. Effect of concentration on the accuracy of convective imaging distribution of a gadolinium-based surrogate tracer. J Neurosurg 2011;115:467–473.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Dickinson PJ, LeCouteur RA, Higgins RJ, et al. Canine model of convection-enhanced delivery of liposomes containing CPT-11 monitored with real-time magnetic resonance imaging: laboratory investigation. J Neurosurg 2008;108:989–998.CrossRefPubMedGoogle Scholar
  31. 31.
    Huynh NT, Passirani C, Allard-Vannier E, et al. Administration-dependent efficacy of ferrociphenol lipid nanocapsules for the treatment of intracranial 9L rat gliosarcoma. Int J Pharm 2012;423:55–62.CrossRefPubMedGoogle Scholar
  32. 32.
    Szerlip NJ, Walbridge S, Yang L, et al. Real-time imaging of convection-enhanced delivery of viruses and virus-sized particles. J Neurosurg 2007;107:560–567.CrossRefPubMedGoogle Scholar
  33. 33.
    Raghavan R, Brady, M. Sampson, JH. Delivering therapy to target: improving the odds for successful drug development. Ther Deliv 2016;7:457–481.CrossRefPubMedGoogle Scholar
  34. 34.
    Sampson JH, Raghavan R, Brady M, Friedman AH, Bigner D. Convection-enhanced delivery. J Neurosurg 2011;115:463–464.CrossRefPubMedGoogle Scholar
  35. 35.
    Reardon DA, Rich JN, Friedman HS, Bigner DD. Recent advances in the treatment of malignant astrocytoma. J Clin Oncol 2006;24:1253–1265.Google Scholar
  36. 36.
    Mehta AI, Choi BD, Raghavan R, et al. Imaging of convection enhanced delivery of toxins in humans. Toxins (Basel) 2011;3:201–206.Google Scholar
  37. 37.
    Healy AT, Vogelbaum MA. Convection-enhanced drug delivery for gliomas. Surg Neurol Int 2015;6(Suppl. 1):S59-S67.Google Scholar
  38. 38.
    Fiandaca MS, Forsayeth JR, Dickinson PJ, Bankiewicz KS. Image-guided convection-enhanced delivery platform in the treatment of neurological diseases. Neurotherapeutics 2008;5:123–127.Google Scholar
  39. 39.
    Casanova F, Carney PR, Sarntinoranont M. Effect of needle insertion speed on tissue injury, stress, and backflow distribution for convection-enhanced delivery in the rat brain. PLOS ONE 2014;9:e94919.Google Scholar
  40. 40.
    Sillay KA, McClatchy SG, Shepherd BA, Venable GT, Fuehrer TS. Image-guided convection-enhanced delivery into agarose gel models of the brain. J Vis Exp 2014(87).Google Scholar
  41. 41.
    Krauze MT, Saito R, Noble C, Tamas M, Bringas J, Park JW, et al. Reflux-free cannula for convection-enhanced high-speed delivery of therapeutic agents. J Neurosurg 2005;103:923–929.Google Scholar
  42. 42.
    Allard E, Passirani C, Benoit JP. Convection-enhanced delivery of nanocarriers for the treatment of brain tumors. Biomaterials 2009;30:2302–2318.Google Scholar
  43. 43.
    Jain RK. Physiological barriers to delivery of monoclonal antibodies and other macromolecules in tumors. Cancer Res 1990;50(3 Suppl.):814s-819s.Google Scholar
  44. 44.
    Jain RK. Transport of molecules in the tumor interstitium: a review. Cancer Res 1987;47:3039–3051.Google Scholar
  45. 45.
    Jain RK. Transport of molecules across tumor vasculature. Cancer Metastasis Rev 1987;6:559–593.Google Scholar
  46. 46.
    Jain RK. Tumor physiology and antibody delivery. Front Radiat Ther Oncol 1990;24:32–46.Google Scholar
  47. 47.
    Jain RK. Vascular and interstitial barriers to delivery of therapeutic agents in tumors. Cancer Metastasis Rev 1990;9:253–266.Google Scholar
  48. 48.
    Jain RK, Baxter LT. Mechanisms of heterogeneous distribution of monoclonal antibodies and other macromolecules in tumors: significance of elevated interstitial pressure. Cancer Res 1988;48:7022–7032.Google Scholar
  49. 49.
    Brady ML, Raghavan R, Alexander A, Kubota K, Sillay K, Emborg ME. Pathways of infusate loss during convection-enhanced delivery into the putamen nucleus. Stereotact Funct Neurosurg 2013;91:69–78.Google Scholar
  50. 50.
    Bidros DS, Liu JK, Vogelbaum MA. Future of convection-enhanced delivery in the treatment of brain tumors. Future Oncol 2010;6:117–125.Google Scholar
  51. 51.
    Bruce JN, Fine RL, Canoll P, et al. Regression of recurrent malignant gliomas with convection-enhanced delivery of topotecan. Neurosurgery 2011;69:1272–1279.Google Scholar
  52. 52.
    Patel SJ, Shapiro WR, Laske DW, Jensen RL, Asher AL, Wessels BW, et al. Safety and feasibility of convection-enhanced delivery of Cotara for the treatment of malignant glioma: initial experience in 51 patients. Neurosurgery 2005;56:1243–1252.Google Scholar
  53. 53.
    Souweidane MM. Editorial: convection-enhanced delivery for diffuse intrinsic pontine glioma. J Neurosurg Pediatr 2014;13:273–274.Google Scholar
  54. 54.
    Ung TH, Malone H, Canoll P, Bruce JN. Convection-enhanced delivery for glioblastoma: targeted delivery of antitumor therapeutics. CNS Oncol 2015;4:225–234.Google Scholar
  55. 55.
    Hadaczek P, Kohutnicka M, Krauze MT, et al. Convection-enhanced delivery of adeno-associated virus type 2 (AAV2) into the striatum and transport of AAV2 within monkey brain. Hum Gene Ther 2006;17:291–302.Google Scholar
  56. 56.
    Krauze MT, Forsayeth J, Yin D, Bankiewicz KS. Convection-enhanced delivery of liposomes to primate brain. Methods Enzymol 2009;465:349–362.Google Scholar
  57. 57.
    Sampson JH, Brady ML, Petry NA, et al. Intracerebral infusate distribution by convection-enhanced delivery in humans with malignant gliomas: descriptive effects of target anatomy and catheter positioning. Neurosurgery 2007;60(2 Suppl. 1):ONS89-98.Google Scholar
  58. 58.
    Vavra M, Ali MJ, Kang EW, et al. Comparative pharmacokinetics of 14C-sucrose in RG-2 rat gliomas after intravenous and convection-enhanced delivery. Neuro Oncol 2004;6:104–112.Google Scholar
  59. 59.
    Geer CP, Grossman SA. Interstitial fluid flow along white matter tracts: a potentially important mechanism for the dissemination of primary brain tumors. J Neurooncol 1997;32:193–201.Google Scholar
  60. 60.
    Sampson JH, Raghavan R, Brady ML, et al. Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions. Neuro Oncol 2007;9:343–353.Google Scholar
  61. 61.
    Voges J, Reszka R, Gossmann A, et al. Imaging-guided convection-enhanced delivery and gene therapy of glioblastoma. Ann Neurol 2003;54:479–487.Google Scholar
  62. 62.
    Linninger AA, Somayaji MR, Mekarski M, Zhang L. Prediction of convection-enhanced drug delivery to the human brain. J Theor Biol 2008;250:125–138.Google Scholar
  63. 63.
    Lonser RR, Warren KE, Butman JA, et al. Real-time image-guided direct convective perfusion of intrinsic brainstem lesions. Technical note. J Neurosurg 2007;107:190–197.Google Scholar
  64. 64.
    Laske DW, Youle RJ, Oldfield EH. Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors. Nat Med 1997;3:1362–1368.Google Scholar
  65. 65.
    Bigner DD. PVSRIPO for Recurrent Glioblastoma (GBM) (PVSRIPO). NCT01491893. Available from: https://clinicaltrials.gov/ct2/show/NCT01491893.
  66. 66.
    Greenfield L, Johnson VG, Youle RJ. Mutations in diphtheria toxin separate binding from entry and amplify immunotoxin selectivity. Science 1987;238:536–539.Google Scholar
  67. 67.
    Johnson VG, Wrobel C, Wilson D, et al. Improved tumor-specific immunotoxins in the treatment of CNS and leptomeningeal neoplasia. J Neurosurg 1989;70:240–248.Google Scholar
  68. 68.
    Larrick JW, Cresswell P. Modulation of cell surface iron transferrin receptors by cellular density and state of activation. J Supramol Struct 1979;11:579–586.Google Scholar
  69. 69.
    Faulk WP, Hsi BL, Stevens PJ. Transferrin and transferrin receptors in carcinoma of the breast. Lancet 1980;2:390–392.Google Scholar
  70. 70.
    Trowbridge IS, Omary MB. Human cell surface glycoprotein related to cell proliferation is the receptor for transferrin. Proc Natl Acad Sci U S A 1981;78:3039–3043.Google Scholar
  71. 71.
    Shindelman JE, Ortmeyer AE, Sussman HH. Demonstration of the transferrin receptor in human breast cancer tissue. Potential marker for identifying dividing cells. Int J Cancer 1981;27:329–334.Google Scholar
  72. 72.
    Klausner RD, Van Renswoude J, Ashwell G, et al. Receptor-mediated endocytosis of transferrin in K562 cells. J Biol Chem 1983;258:4715–4724.Google Scholar
  73. 73.
    Prior R, Reifenberger G, Wechsler W. Transferrin receptor expression in tumours of the human nervous system: relation to tumour type, grading and tumour growth fraction. Virchows Arch A Pathol Anat Histopathol 1990;416:491–496.Google Scholar
  74. 74.
    Gatter KC, Brown G, Trowbridge IS, Woolston RE, Mason DY. Transferrin receptors in human tissues: their distribution and possible clinical relevance. J Clin Pathol 1983;36:539–545.Google Scholar
  75. 75.
    Mueller S, Polley MY, Lee B, et al. Effect of imaging and catheter characteristics on clinical outcome for patients in the PRECISE study. J Neurooncol 2011;101:267–277.Google Scholar
  76. 76.
    Joshi BH, Plautz GE, Puri RK. Interleukin-13 receptor alpha chain: a novel tumor-associated transmembrane protein in primary explants of human malignant gliomas. Cancer Res 2000;60:1168–1172.Google Scholar
  77. 77.
    Liu H, Jacobs BS, Liu J, et al. Interleukin-13 sensitivity and receptor phenotypes of human glial cell lines: non-neoplastic glia and low-grade astrocytoma differ from malignant glioma. Cancer Immunol Immunother 2000;49:319–324.Google Scholar
  78. 78.
    Debinski W, Obiri NI, Pastan I, Puri RK. A novel chimeric protein composed of interleukin 13 and Pseudomonas exotoxin is highly cytotoxic to human carcinoma cells expressing receptors for interleukin 13 and interleukin 4. J Biol Chem 1995;270:16775–16780.Google Scholar
  79. 79.
    Husain SR, Joshi BH, Puri RK. Interleukin-13 receptor as a unique target for anti-glioblastoma therapy. Int J Cancer 2001;92:168–175.Google Scholar
  80. 80.
    Sampson JH, Archer G, Pedain C, et al. Poor drug distribution as a possible explanation for the results of the PRECISE trial. J Neurosurg 2010;113:301–309.Google Scholar
  81. 81.
    Kunwar S, Prados MD, Chang SM, et al. Direct intracerebral delivery of cintredekin besudotox (IL13-PE38QQR) in recurrent malignant glioma: a report by the Cintredekin Besudotox Intraparenchymal Study Group. J Clin Oncol 2007;25:837–844.Google Scholar
  82. 82.
    Pommier Y. Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer 2006;6:789–802.Google Scholar
  83. 83.
    Burch PA, Bernath AM, Cascino TL, et al. A North Central Cancer Treatment Group phase II trial of topotecan in relapsed gliomas. Invest New Drugs 2000;18:275–280.Google Scholar
  84. 84.
    Lopez KA, Tannenbaum AM, Assanah MC, et al. Convection-enhanced delivery of topotecan into a PDGF-driven model of glioblastoma prolongs survival and ablates both tumor-initiating cells and recruited glial progenitors. Cancer Res 2011;71:3963–3971.Google Scholar
  85. 85.
    Oberg JA, Dave AN, Bruce JN, Sands SA. Neurocognitive functioning and quality of life in patients with recurrent malignant gliomas treated on a phase Ib trial evaluating topotecan by convection-enhanced delivery. Neurooncol Pract 2014;1:94–100.Google Scholar
  86. 86.
    Lidar Z, Mardor Y, Jonas T, et al. Convection-enhanced delivery of paclitaxel for the treatment of recurrent malignant glioma: a phase I/II clinical study. J Neurosurg 2004;100:472–479.Google Scholar
  87. 87.
    Cheson BD. Clinical trials referral resource. Update on taxol trials. Oncology (Williston Park) 1993;7:63.Google Scholar
  88. 88.
    Terzis AJ, Thorsen F, Heese O, et al. Proliferation, migration and invasion of human glioma cells exposed to paclitaxel (Taxol) in vitro. Br J Cancer 1997;75:1744–1752.Google Scholar
  89. 89.
    Monk BJ, Walker JL, Tewari K, Ramsinghani NS, Nisar Syed AM, DiSaia PJ. Open interstitial brachytherapy for the treatment of local-regional recurrences of uterine corpus and cervix cancer after primary surgery. Gynecol Oncol 1994;52:222–228.Google Scholar
  90. 90.
    Chang MY, Soong YK, Huang CC. Comparison of histocompatibility between couples with idiopathic recurrent spontaneous abortion and normal multipara. J Formos Med Assoc 1991;90:153–159.Google Scholar
  91. 91.
    Fetell MR, Grossman SA, Fisher JD, et al. Preirradiation paclitaxel in glioblastoma multiforme: efficacy, pharmacology, and drug interactions. New Approaches to Brain Tumor Therapy Central Nervous System Consortium. J Clin Oncol 1997;15:3121–3128.Google Scholar
  92. 92.
    Jordan MA, Toso RJ, Thrower D, Wilson L. Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations. Proc Natl Acad Sci U S A 1993;90:9552–9556.Google Scholar
  93. 93.
    Warren KE. Diffuse intrinsic pontine glioma: poised for progress. Front Oncol 2012;2:205.Google Scholar
  94. 94.
    Occhiogrosso G, Edgar MA, Sandberg DI, Souweidane MM. Prolonged convection-enhanced delivery into the rat brainstem. Neurosurgery 2003;52:388–393.Google Scholar
  95. 95.
    Frazier JL, Lee J, Thomale UW, Noggle JC, Cohen KJ, Jallo GI. Treatment of diffuse intrinsic brainstem gliomas: failed approaches and future strategies. J Neurosurg Pediatr 2009;3:259–269.Google Scholar
  96. 96.
    Khatua S, Moore KR, Vats TS, Kestle JR. Diffuse intrinsic pontine glioma-current status and future strategies. Childs Nerv Syst 2011;27:1391–1397.Google Scholar
  97. 97.
    Sandberg DI, Edgar MA, Souweidane MM. Convection-enhanced delivery into the rat brainstem. J Neurosurg 2002;96:885–891.Google Scholar
  98. 98.
    Anderson RC, Kennedy B, Yanes CL, et al. Convection-enhanced delivery of topotecan into diffuse intrinsic brainstem tumors in children. J Neurosurg Pediatr 2013;11:289–295.Google Scholar
  99. 99.
    Moore AE. Effect of inoculation of the viruses of influenza A and herpes simplex on the growth of transplantable tumors in mice. Cancer 1949;2:516–524.Google Scholar
  100. 100.
    Andtbacka RH, Kaufman HL, Collichio F, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol 2015;33:2780–2788.Google Scholar
  101. 101.
    Kaufman HL, Kohlhapp FJ, Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev Drug Discov 2015;14:642–662.Google Scholar
  102. 102.
    Moore AE. The destructive effect of the virus of Russian Far East encephalitis on the transplantable mouse sarcoma 180. Cancer 1949;2:525–534.Google Scholar
  103. 103.
    Duke Today. Poliovirus vaccine trial shows early promise for recurrent glioblastoma. Medicine, Academics, Research. Available at: https://today.duke.edu/2013/07/poliovirus-vaccine-trial-shows-promise-recurrent-glioblastoma. Accessed February 26, 2017.
  104. 104.
    Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 1993;260:1130–1132.Google Scholar
  105. 105.
    Background Information on GDNF – a timeline: Parkinson's Disease Foundation. Available at: http://www.pdf.org/en/science_news/release/pr_1216665220. Accessed June 26, 2016.
  106. 106.
    Gill SS, Patel NK, Hotton GR, et al. Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat Med 2003;9:589–595.Google Scholar
  107. 107.
    Salvatore MF, Ai Y, Fischer B, et al. Point source concentration of GDNF may explain failure of phase II clinical trial. Exp Neurol 2006;202:497–505.Google Scholar
  108. 108.
    Morrison PF, Lonser RR, Oldfield EH. Convective delivery of glial cell line-derived neurotrophic factor in the human putamen. J Neurosurg 2007;107:74–83.Google Scholar
  109. 109.
    Bartus RT, Herzog CD, Bishop K, et al. Issues regarding gene therapy products for Parkinson's disease: the development of CERE-120 (AAV-NTN) as one reference point. Parkinsonism Relat Disord 2007;13(Suppl. 3):S469-S477.Google Scholar
  110. 110.
    Olanow CW, Kieburtz K, Schapira AH. Why have we failed to achieve neuroprotection in Parkinson's disease? Ann Neurol 2008;64(Suppl. 2):S101-S110.Google Scholar
  111. 111.
    Bartus RT, Weinberg MS, Samulski RJ. Parkinson's disease gene therapy: success by design meets failure by efficacy. Mol Ther 2014;22:487–497.Google Scholar
  112. 112.
    Warren Olanow C, Bartus RT, Baumann TL, et al. Gene delivery of neurturin to putamen and substantia nigra in Parkinson disease: a double-blind, randomized, controlled trial. Ann Neurol 2015;78:248–257.Google Scholar
  113. 113.
    Debinski W, Tatter SB. Convection-enhanced delivery for the treatment of brain tumors. Expert Rev Neurother 2009;9:1519–1527.Google Scholar
  114. 114.
    Chen MY, Lonser RR, Morrison PF, Governale LS, Oldfield EH. Variables affecting convection-enhanced delivery to the striatum: a systematic examination of rate of infusion, cannula size, infusate concentration, and tissue-cannula sealing time. J Neurosurg 1999;90:315–320.Google Scholar
  115. 115.
    Morrison PF, Chen MY, Chadwick RS, Lonser RR, Oldfield EH. Focal delivery during direct infusion to brain: role of flow rate, catheter diameter, and tissue mechanics. Am J Physiol 1999;277:R1218-R1229.Google Scholar
  116. 116.
    Oh S, Odland R, Wilson SR, et al. Improved distribution of small molecules and viral vectors in the murine brain using a hollow fiber catheter. J Neurosurg 2007;107:568–577.Google Scholar
  117. 117.
    Olson JJ, Zhang Z, Dillehay D, Stubbs J. Assessment of a balloon-tipped catheter modified for intracerebral convection-enhanced delivery. J Neurooncol 2008;89:159–168.Google Scholar
  118. 118.
    Olivi A, Grossman SA, Tatter S, et al. Dose escalation of carmustine in surgically implanted polymers in patients with recurrent malignant glioma: a New Approaches to Brain Tumor Therapy CNS Consortium trial. J Clin Oncol 2003;21:1845–1849.Google Scholar
  119. 119.
    Sonabend AM, Stuart RM, Yun J, et al. Prolonged intracerebral convection-enhanced delivery of topotecan with a subcutaneously implantable infusion pump. Neuro Oncol 2011;13:886–893.Google Scholar
  120. 120.
    Mehta AI, Choi BD, Ajay D, et al. Convection enhanced delivery of macromolecules for brain tumors. Curr Drug Discov Technol 2012;9:305–310.Google Scholar
  121. 121.
    Saito R, Bringas JR, McKnight TR, et al. Distribution of liposomes into brain and rat brain tumor models by convection-enhanced delivery monitored with magnetic resonance imaging. Cancer Res 2004;64:2572–2579.Google Scholar
  122. 122.
    Raghavan R, Mikaelian S, Brady M, Chen ZJ. Fluid infusions from catheters into elastic tissue: I. Azimuthally symmetric backflow in homogeneous media. Phys Med Biol 2010;55:281–304.Google Scholar
  123. 123.
    Mardor Y, Rahav O, Zauberman Y, et al. Convection-enhanced drug delivery: increased efficacy and magnetic resonance image monitoring. Cancer Res 2005;65:6858–6863.Google Scholar
  124. 124.
    Brady M, Raghavan R, Chen ZJ, Broaddus WC. Quantifying fluid infusions and tissue expansion in brain. IEEE Trans Biomed Eng 2011;58.Google Scholar
  125. 125.
    Sampson JH, Reardon DA, Friedman AH, et al. Sustained radiographic and clinical response in patient with bifrontal recurrent glioblastoma multiforme with intracerebral infusion of the recombinant targeted toxin TP-38: case study. Neuro Oncol 2005;7:90–96.Google Scholar
  126. 126.
    Mardor Y, Roth Y, Lidar Z, et al. Monitoring response to convection-enhanced taxol delivery in brain tumor patients using diffusion-weighted magnetic resonance imaging. Cancer Res 2001;61:4971–4973.Google Scholar
  127. 127.
    Sampson JH, Raghavan R, Provenzale JM, et al. Induction of hyperintense signal on T2-weighted MR images correlates with infusion distribution from intracerebral convection-enhanced delivery of a tumor-targeted cytotoxin. AJR Am J Roentgenol 2007;188:703–709.Google Scholar

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2017

Authors and Affiliations

  1. 1.Department of Neurological SurgeryColumbia University Medical CenterNew YorkUSA

Personalised recommendations