Delivery of chemotherapeutics across the blood-brain barrier: Challenges and advances

Advances in Pharmacology

Volumn 71, Issue , 2014, Pages 203-243

  Doolittle, Nancy D ^a   Muldoon, Leslie L ^a,b   Culp, Aliana Y ^a   Neuwelt, Edward A ^a,b,c  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^b OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^c PORTLAND VA MEDICAL CENTER   (United States)

Author keywords

Blood brain barrier; Blood brain barrier disruption; Chemoprotection; Monoclonal antibody; Neuroimaging; Primary central nervous system lymphoma

Indexed keywords

ANTINEOPLASTIC AGENT; CARBOPLATIN; CONTRAST MEDIUM; FERUMOXYTOL; MANNITOL; METHOTREXATE; MONOCLONAL ANTIBODY; PLATINUM; RITUXIMAB; SODIUM THIOSULFATE; THIOL DERIVATIVE;

ARTICLE; BLOOD BRAIN BARRIER; BRAIN TUMOR; CANCER PATIENT; CANCER SURVIVOR; CENTRAL NERVOUS SYSTEM METASTASIS; COGNITION; COMPARTMENT MODEL; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG MEGADOSE; ENDOTHELIUM CELL; HEARING IMPAIRMENT; HUMAN; NEUROIMAGING; NEUROTOXICITY; NONHUMAN; OLIGODENDROGLIOMA; OVERALL SURVIVAL; PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA; TIGHT JUNCTION; TREATMENT OUTCOME; TREATMENT RESPONSE; TUMOR VASCULARIZATION; UNSPECIFIED SIDE EFFECT; ANIMAL; CENTRAL NERVOUS SYSTEM NEOPLASMS; DIAGNOSTIC USE; LYMPHOMA, B-CELL; METABOLISM; NUCLEAR MAGNETIC RESONANCE IMAGING;

ANIMALS; ANTINEOPLASTIC AGENTS; BLOOD-BRAIN BARRIER; CENTRAL NERVOUS SYSTEM NEOPLASMS; CONTRAST MEDIA; HUMANS; LYMPHOMA, B-CELL; MAGNETIC RESONANCE IMAGING;

EID: 84907997688     PISSN: 10543589     EISSN: 15578925     Source Type: Book Series    
DOI: 10.1016/bs.apha.2014.06.002     Document Type: Chapter

References (84)

1. Angelov L., Doolittle N.D., Kraemer D.F., Siegal T., Barnett G.H., Peereboom D.M., et al. Blood-brain barrier disruption and intra-arterial methotrexate-based therapy for newly diagnosed primary CNS lymphoma: A multi-institutional experience. Journal of Clinical Oncology 2009, 27(21):3503-3509.
2. Batchelor T.T., Grossman S.A., Mikkelsen T., Ye X., Desideri S., Lesser G.J. Rituximab monotherapy for patients with recurrent primary CNS lymphoma. Neurology 2011, 76(10):929-930.
3. Brightman M.W., Hori M., Rapoport S.I., Reese T.S., Westergaard E. Osmotic opening of tight junctions in cerebral endothelium. Journal of Comparative Neurology 1973, 152(4):317-325.
4. Brightman M.W., Reese T.S. Junctions between intimately apposed cell membranes in the vertebrate brain. Journal of Cell Biology 1969, 40(3):648-677.
5. Christen T., Ni W., Qiu D., Schmiedeskamp H., Bammer R., Moseley M., et al. High-resolution cerebral blood volume imaging in humans using the blood pool contrast agent ferumoxytol. Magnetic Resonance in Medicine 2013, 70(3):705-710. 10.1002/mrm.24500.
6. Coiffier B., Lepage E., Briere J., Herbrecht R., Tilly H., Bouabdallah R., et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. New England Journal of Medicine 2002, 346(4):235-242.
7. Correa D.D., Shi W., Abrey L.E., Deangelis L.M., Omuro A.M., Deutsch M.B., et al. Cognitive functions in primary CNS lymphoma after single or combined modality regimens. Neuro-Oncology 2012, 14(1):101-108.
8. Dahlborg S.A., Henner W.D., Crossen J.R., Tableman C.M., Petrillo A., Braziel R., et al. Non-AIDS primary CNS lymphoma: First example of a durable response in a primary brain tumor using enhanced chemotherapy delivery without cognitive loss and without radiotherapy. The Cancer Journal from Scientific American 1996, 2(3):166-174.
9. Dahlborg S.A., Petrillo A., Crossen J.R., Roman-Goldstein S., Doolittle N.D., Fuller K.H., et al. The potential for complete and durable response in nonglial primary brain tumors in children and young adults with enhanced chemotherapy delivery. The Cancer Journal from Scientific American 1998, 4(2):110-124.
10. D'Arceuil H., Coimbra A., Triano P., Dougherty M., Mello J., Moseley M., et al. Ferumoxytol enhanced resting state fMRI and relative cerebral blood volume mapping in normal human brain. NeuroImage 2013, 83:200-209.
11. Dickey D.T., Dickey D.T., Muldoon L.L., Doolittle N.D., Peterson D.R., Kraemer D.F., et al. Effect of N-acetylcysteine route of administration on chemoprotection against cisplatin-induced toxicity in rat models. Cancer Chemotherapy and Pharmacology 2008, 62(2):235-241.
12. Dickey D.T., Muldoon L.L., Kraemer D.F., Neuwelt E.A. Protection against cisplatin-induced ototoxicity by N-acetylcysteine in a rat model. Hearing Research 2004, 193(1-2):25-30.
13. Dickey D.T., Wu Y.J., Muldoon L.L., Neuwelt E.A. Protection against cisplatin-induced toxicities by N-acetylcysteine and sodium thiosulfate as assessed at the molecular, cellular, and in vivo levels. Journal of Pharmacology and Experimental Therapeutics 2005, 314(3):1052-1058.
14. Doolittle N.D., Abrey L.E., Shenkier T.N., Tali S., Bromberg J.E., Neuwelt E.A., et al. Brain parenchyma involvement as isolated central nervous system relapse of systemic non-Hodgkin lymphoma: An International Primary CNS Lymphoma Collaborative Group report. Blood 2008, 111(3):1085-1093.
15. Doolittle N.D., Dosa E., Fu R., Muldoon L.L., Maron L.M., Lubow M.A., et al. Preservation of cognitive function in primary CNS lymphoma survivors a median of 12 years after enhanced chemotherapy delivery. Journal of Clinical Oncology 2013, 31(31):4026-4027.
16. Doolittle N.D., Fu R., Muldoon L.L., Tyson R.M., Lacy C., Neuwelt E.A. Rituximab in combination with methotrexate-based chemotherapy with blood-brain barrier disruption in newly diagnosed primary CNS lymphoma. Hematological Oncology 2013, 31(S1):179.
17. Doolittle N.D., Jahnke K., Belanger R., Ryan D.A., Nance R.W., Lacy C.A., et al. Potential of chemo-immunotherapy and radioimmunotherapy in relapsed primary central nervous system (CNS) lymphoma. Leukemia and Lymphoma 2007, 48(9):1712-1720.
18. Doolittle N.D., Korfel A., Lubow M.A., Schorb E., Schlegel U., Rogowski S., et al. Long-term cognitive function, neuroimaging, and quality of life in primary CNS lymphoma. Neurology 2013, 81(1):84-92.
19. Doolittle N.D., Miner M.E., Hall W.A., Siegal T., Jerome E., Osztie E., et al. Safety and efficacy of a multicenter study using intraarterial chemotherapy in conjunction with osmotic opening of the blood-brain barrier for the treatment of patients with malignant brain tumors. Cancer 2000, 88(3):637-647.
20. Doolittle N.D., Muldoon L.L., Brummett R.E., Tyson R.M., Lacy C., Bubalo J.S., et al. Delayed sodium thiosulfate as an otoprotectant against carboplatin-induced hearing loss in patients with malignant brain tumors. Clinical Cancer Research 2001, 7(3):493-500.
21. Doolittle N.D., Tyson R.M., Lacy C., Quipotla J., Kraemer D.F., Deloughery T.G., et al. Potential role of delayed sodium thiosulfate as protectant against severe carboplatin-induced thrombocytopenia in patients with malignant brain tumors. Blood 2001, 98(11):37a-38a.
22. Dosa E., Guillaume D.J., Haluska M., Lacy C.A., Hamilton B.E., Njus J.M., et al. Magnetic resonance imaging of intracranial tumors: Intra-patient comparison of gadoteridol and ferumoxytol. Neuro-Oncology 2011, 13(2):251-260.
23. Dosa E., Tuladhar S., Muldoon L.L., Hamilton B.E., Rooney W.D., Neuwelt E.A. MRI using ferumoxytol improves the visualization of central nervous system vascular malformations. Stroke 2011, 42(6):1581-1588.
24. Farrell B.T., Hamilton B.E., Dosa E., Rimely E., Nasseri M., Gahramanov S., et al. Using iron oxide nanoparticles to diagnose CNS inflammatory diseases and PCNSL. Neurology 2013, 81(3):256-263.
25. Fortin D., McCormick C.I., Remsen L.G., Nixon R., Neuwelt E.A. Unexpected neurotoxicity of etoposide phosphate administered in combination with other chemotherapeutic agents after blood-brain barrier modification to enhance delivery, using propofol for general anesthesia, in a rat model. Neurosurgery 2000, 47(1):199-207.
26. Freyer D.R. The effects of sodium thiosulfate (STS) on cisplatin-induced hearing loss: A report from the Children's Oncology Group. Journal of Clinical Oncology 2014, 32:5s. (suppl: abstr 10017).
27. Gahramanov S., Muldoon L.L., Li X., Neuwelt E.A. Improved perfusion MR imaging assessment of intracerebral tumor blood volume and antiangiogenic therapy efficacy in a rat model with ferumoxytol. Radiology 2011, 261(3):796-804.
28. Gahramanov S., Muldoon L.L., Varallyay C.G., Li X., Kraemer D.F., Fu R., et al. Pseudoprogression of glioblastoma after chemo- and radiation therapy: Diagnosis by using dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging with ferumoxytol versus gadoteridol and correlation with survival. Radiology 2013, 266(3):842-852.
29. Gahramanov S., Raslan A.M., Muldoon L.L., Hamilton B.E., Rooney W.D., Varallyay C.G., et al. Potential for differentiation of pseudoprogression from true tumor progression with dynamic susceptibility-weighted contrast-enhanced magnetic resonance imaging using ferumoxytol vs. gadoteridol: A pilot study. International Journal of Radiation Oncology, Biology, Physics 2011, 79(2):514-523.
30. Groothuis D.R., Benalcazar H., Allen C.V., Wise R.M., Dills C., Dobrescu C., et al. Comparison of cytosine arabinoside delivery to rat brain by intravenous, intrathecal, intraventricular and intraparenchymal routes of administration. Brain Research 2000, 856(1-2):281-290.
31. Guillaume D.J., Doolittle N.D., Gahramanov S., Hedrick N.A., Delashaw J.B., Neuwelt E.A. Intra-arterial chemotherapy with osmotic blood-brain barrier disruption for aggressive oligodendroglial tumors: Results of a phase I study. Neurosurgery 2010, 66(1):48-58. discussion 58.
32. Hamilton B.E., Nesbit G.M., Dosa E., Gahramanov S., Rooney B., Nesbit E.G., et al. Comparative analysis of ferumoxytol and gadoteridol enhancement using T1- and T2-weighted MRI in neuroimaging. AJR. American Journal of Roentgenology 2011, 197(4):981-988.
33. Harder H., Holtel H., Bromberg J.E., Poortmans P., Haaxma-Reiche H., Kluin-Nelemans H.C., et al. Cognitive status and quality of life after treatment for primary CNS lymphoma. Neurology 2004, 62(4):544-547.
34. Harned T.M., Kalous O., Neuwelt A., Loera J., Ji L., Iovine P., et al. Sodium thiosulfate administered six hours after cisplatin does not compromise antineuroblastoma activity. Clinical Cancer Research 2008, 14(2):533-540.
35. Jahnke K., Kraemer D.F., Knight K.R., Fortin D., Bell S., Doolittle N.D., et al. Intraarterial chemotherapy and osmotic blood-brain barrier disruption for patients with embryonal and germ cell tumors of the central nervous system. Cancer 2008, 112(3):581-588.
36. Jahnke K., Muldoon L.L., Varallyay C.G., Lewin S.J., Brown R.D., Kraemer D.F., et al. Efficacy and MRI of rituximab and methotrexate treatment in a nude rat model of CNS lymphoma. Neuro-Oncology 2009, 11(5):503-513.
37. Kroll R.A., Neuwelt E.A. Outwitting the blood-brain barrier for therapeutic purposes: Osmotic opening and other means. Neurosurgery 1998, 42(5):1083-1099. discussion 1099-1100.
38. Maibach R., Childs M., Rajput K., Neuwelt E.A., Roebuck D., Sullivan M.J., et al. SIOPEL6: A multicenter open-label randomized phase III trial of the efficacy of sodium thiosulphate (STS) in reducing ototoxicity in patients receiving cisplatin (Cis) monotherapy for standard-risk hepatoblastoma (SR-HB). Journal of Clinical Oncology 2014, 32:5s. (suppl; asbtr TPS 10094).
39. Maza S., Kiewe P., Munz D.L., Korfel A., Hamm B., Jahnke K., et al. First report on a prospective trial with yttrium-90-labeled ibritumomab tiuxetan (Zevalin) in primary CNS lymphoma. Neuro-Oncology 2009, 11(4):423-429.
40. McAllister L.D., Doolittle N.D., Guastadisegni P.E., Kraemer D.F., Lacy C.A., Crossen J.R., et al. Cognitive outcomes and long-term follow-up results after enhanced chemotherapy delivery for primary central nervous system lymphoma. Neurosurgery 2000, 46(1):51-60. discussion 60-51.
41. Morris P.G., Abrey L.E. Therapeutic challenges in primary CNS lymphoma. Lancet Neurology 2009, 8(6):581-592.
42. Muldoon L.L., Alvarez J.I., Begley D.J., Boado R.J., Del Zoppo G.J., Doolittle N.D., et al. Immunologic privilege in the central nervous system and the blood-brain barrier. Journal of Cerebral Blood Flow and Metabolism 2013, 33(1):13-21.
43. Muldoon L.L., Gahramanov S., Li X., Marshall D.J., Kraemer D.F., Neuwelt E.A. Dynamic magnetic resonance imaging assessment of vascular targeting agent effects in rat intracerebral tumor models. Neuro-Oncology 2011, 13(1):51-60.
44. Muldoon L.L., Lewin S.J., Dosa E., Kraemer D.F., Pagel M.A., Doolittle N.D., et al. Imaging and therapy with rituximab anti-CD20 immunotherapy in an animal model of central nervous system lymphoma. Clinical Cancer Research 2011, 17(8):2207-2215.
45. Muldoon L.L., Pagel M.A., Kroll R.A., Brummett R.E., Doolittle N.D., Zuhowski E.G., et al. Delayed administration of sodium thiosulfate in animal models reduces platinum ototoxicity without reduction of antitumor activity. Clinical Cancer Research 2000, 6(1):309-315.
46. Muldoon L.L., Pagel M.A., Kroll R.A., Roman-Goldstein S., Jones R.S., Neuwelt E.A. A physiological barrier distal to the anatomic blood-brain barrier in a model of transvascular delivery. American Journal of Neuroradiology 1999, 20(2):217-222.
47. Muldoon L.L., Sandor M., Pinkston K.E., Neuwelt E.A. Imaging, distribution, and toxicity of superparamagnetic iron oxide magnetic resonance nanoparticles in the rat brain and intracerebral tumor. Neurosurgery 2005, 57(4):785-796. discussion 785-796.
48. Muldoon L.L., Soussain C., Jahnke K., Johanson C., Siegal T., Smith Q.R., et al. Chemotherapy delivery issues in central nervous system malignancy: A reality check. Journal of Clinical Oncology 2007, 25(16):2295-2305.
49. Muldoon L.L., Walker-Rosenfeld S.L., Hale C., Purcell S.E., Bennett L.C., Neuwelt E.A. Rescue from enhanced alkylator-induced cell death with low molecular weight sulfur-containing chemoprotectants. Journal of Pharmacology and Experimental Therapeutics 2001, 296(3):797-805.
50. th Annual Meeting of the American Association for Cancer Research 2014, San Diego, CA, Philadelphia.
51. Nakagawa H., Fujita T., Izumoto S., Kubo S., Nakajima Y., Tsuruzono K., et al. Cis-diamminedichloroplatinum (CDDP) therapy for brain metastasis of lung cancer. Journal of Neuro-Oncology 1993, 16(1):61-67.
52. Implications of the blood-brain barrier and its manipulation 1989, Vol. 2. Plenum Publishing Corporation, New York.
53. Neuwelt E.A. Mechanisms of disease: The blood-brain barrier. Neurosurgery 2004, 54(1):131-140. discussion 141-132.
54. Neuwelt E.A., Balaban E., Diehl J., Hill S., Frenkel E. Successful treatment of primary central nervous system lymphomas with chemotherapy after osmotic blood-brain barrier opening. Neurosurgery 1983, 12(6):662-671.
55. Neuwelt E.A., Barnett P.A., Glasberg M., Frenkel E.P. Pharmacology and neurotoxicity of cis-diamminedichloroplatinum, bleomycin, 5-fluorouracil, and cyclophosphamide administration following osmotic blood-brain barrier modification. Cancer Research 1983, 43(11):5278-5285.
56. Neuwelt E.A., Barnett P.A., McCormick C.I., Remsen L.G., Kroll R.A., Sexton G. Differential permeability of a human brain tumor xenograft in the nude rat: Impact of tumor size and method of administration on optimizing delivery of biologically diverse agents. Clinical Cancer Research 1998, 4(6):1549-1555.
57. Neuwelt E.A., Bauer B., Fahlke C., Fricker G., Iadecola C., Janigro D., et al. Engaging neuroscience to advance translational research in brain barrier biology. Nature Reviews Neuroscience 2011, 12(3):169-182.
58. Neuwelt E.A., Brummett R.E., Doolittle N.D., Muldoon L.L., Kroll R.A., Pagel M.A., et al. First evidence of otoprotection against carboplatin-induced hearing loss with a two-compartment system in patients with central nervous system malignancy using sodium thiosulfate. Journal of Pharmacology and Experimental Therapeutics 1998, 286(1):77-84.
59. Neuwelt E.A., Brummett R.E., Remsen L.G., Kroll R.A., Pagel M.A., McCormick C.I., et al. In vitro and animal studies of sodium thiosulfate as a potential chemoprotectant against carboplatin-induced ototoxicity. Cancer Research 1996, 56(4):706-709.
60. Neuwelt E.A., Frenkel E.P., Rapoport S., Barnett P. Effect of osmotic blood-brain barrier disruption on methotrexate pharmacokinetics in the dog. Neurosurgery 1980, 7(1):36-43.
61. Neuwelt E.A., Goldman D.L., Dahlborg S.A., Crossen J., Ramsey F., Roman-Goldstein S., et al. Primary CNS lymphoma treated with osmotic blood-brain barrier disruption: Prolonged survival and preservation of cognitive function. Journal of Clinical Oncology 1991, 9(9):1580-1590.
62. Neuwelt E.A., Hamilton B.E., Varallyay C.G., Rooney W.R., Edelman R.D., Jacobs P.M., et al. Ultrasmall superparamagnetic iron oxides (USPIOs): A future alternative magnetic resonance (MR) contrast agent for patients at risk for nephrogenic systemic fibrosis (NSF)?. Kidney International 2009, 75(5):465-474.
63. Neuwelt E.A., Pagel M., Barnett P., Glassberg M., Frenkel E.P. Pharmacology and toxicity of intracarotid adriamycin administration following osmotic blood-brain barrier modification. Cancer Research 1981, 41(11 Pt. 1):4466-4470.
64. Neuwelt E.A., Pagel M.A., Hasler B.P., Deloughery T.G., Muldoon L.L. Therapeutic efficacy of aortic administration of N-acetylcysteine as a chemoprotectant against bone marrow toxicity after intracarotid administration of alkylators, with or without glutathione depletion in a rat model. Cancer Research 2001, 61(21):7868-7874.
65. Neuwelt E.A., Pagel M.A., Kraemer D.F., Peterson D.R., Muldoon L.L. Bone marrow chemoprotection without compromise of chemotherapy efficacy in a rat brain tumor model. Journal of Pharmacology and Experimental Therapeutics 2004, 309(2):594-599.
66. Neuwelt E.A., Varallyay C.G., Manninger S., Solymosi D., Haluska M., Hunt M.A., et al. The potential of ferumoxytol nanoparticle magnetic resonance imaging, perfusion, and angiography in central nervous system malignancy: A pilot study. Neurosurgery 2007, 60(4):601-611. discussion 611-602.
67. Rapoport S.I., Robinson P.J. Tight-junctional modification as the basis of osmotic opening of the blood-brain barrier. Annals of the New York Academy of Sciences 1986, 481:250-267.
68. Remsen L.G., Marquez C., Garcia R., Thrun L.A., Neuwelt E.A. Efficacy after sequencing of brain radiotherapy and enhanced antibody targeted chemotherapy delivery in a rodent human lung cancer brain xenograft model. International Journal of Radiation Oncology, Biology, Physics 2001, 51(4):1045-1049.
69. Remsen L.G., McCormick C.I., Sexton G., Pearse H.D., Garcia R., Mass M., et al. Long-term toxicity and neuropathology associated with the sequencing of cranial irradiation and enhanced chemotherapy delivery. Neurosurgery 1997, 40(5):1034-1040. discussion 1040-1032.
70. Remsen L.G., McCormick C.I., Sexton G., Pearse H.D., Garcia R., Neuwelt E.A. Decreased delivery and acute toxicity of cranial irradiation and chemotherapy given with osmotic blood-brain barrier disruption in a rodent model: The issue of sequence. Clinical Cancer Research 1995, 1(7):731-739.
71. Remsen L.G., Pagel M.A., McCormick C.I., Fiamengo S.A., Sexton G., Neuwelt E.A. The influence of anesthetic choice, PaCO2, and other factors on osmotic blood-brain barrier disruption in rats with brain tumor xenografts. Anesthesia and Analgesia 1999, 88(3):559-567.
72. Remsen L.G., Trail P.A., Hellstrom I., Hellstrom K.E., Neuwelt E.A. Enhanced delivery improves the efficacy of a tumor-specific doxorubicin immunoconjugate in a human brain tumor xenograft model. Neurosurgery 2000, 46(3):704-709.
73. Roman-Goldstein S., Clunie D.A., Stevens J., Hogan R., Monard J., Ramsey F., et al. Osmotic blood-brain barrier disruption: CT and radionuclide imaging. American Journal of Neuroradiology 1994, 15(3):581-590.
74. Savaraj N., Lu K., Feun L.G., Burgess M.A., Loo T.L. Comparison of CNS penetration, tissue distribution, and pharmacology of VP 16-213 by intracarotid and intravenous administration in dogs. Cancer Investigation 1987, 5(1):11-16.
75. Soussain C., Muldoon L.L., Varallyay C., Jahnke K., DePaula L., Neuwelt E.A. Characterization and magnetic resonance imaging of a rat model of human B-cell central nervous system lymphoma. Clinical Cancer Research 2007, 13(8):2504-2511.
76. Thiel E., Korfel A., Martus P., Kanz L., Griesinger F., Rauch M., et al. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): A phase 3, randomised, non-inferiority trial. Lancet Oncology 2010, 11(11):1036-1047.
77. Thompson E.M., Pishko G.L., Muldoon L.L., Neuwelt E.A. Inhibition of SUR1 decreases the vascular permeability of cerebral metastases. Neoplasia 2013, 15(5):535-543.
78. Tyson R.M., Siegal T., Doolittle N.D., Lacy C., Kraemer D.F., Neutwelt E.A. Current status and future of relapsed primary central nervous system lymphoma (PCNSL). Leukemia and Lymphoma 2003, 44(4):627-633.
79. Varallyay C.G., Muldoon L.L., Gahramanov S., Wu Y.J., Goodman J.A., Li X., et al. Dynamic MRI using iron oxide nanoparticles to assess early vascular effects of antiangiogenic versus corticosteroid treatment in a glioma model. Journal of Cerebral Blood Flow and Metabolism 2009, 29(4):853-860.
80. Varallyay C.G., Nesbit E., Fu R., Gahramanov S., Moloney B., Earl E., et al. High-resolution steady-state cerebral blood volume maps in patients with central nervous system neoplasms using ferumoxytol, a superparamagnetic iron oxide nanoparticle. Journal of Cerebral Blood Flow and Metabolism 2013, 33(5):780-786.
81. Weinstein J.S., Varallyay C.G., Dosa E., Gahramanov S., Hamilton B., Rooney W.D., et al. Superparamagnetic iron oxide nanoparticles: Diagnostic magnetic resonance imaging and potential therapeutic applications in neurooncology and central nervous system inflammatory pathologies, a review. Journal of Cerebral Blood Flow and Metabolism 2010, 30(1):15-35.
82. Wu Y.J., Muldoon L.L., Gahramanov S., Kraemer D.F., Marshall D.J., Neuwelt E.A. Targeting alphaV-integrins decreased metastasis and increased survival in a nude rat breast cancer brain metastasis model. Journal of Neuro-Oncology 2012, 110(1):27-36.
83. Wu Y.J., Muldoon L.L., Neuwelt E.A. The chemoprotective agent N-acetylcysteine blocks cisplatin-induced apoptosis through caspase signaling pathway. Journal of Pharmacology and Experimental Therapeutics 2005, 312(2):424-431.
84. Zucchetti M., Rossi C., Knerich R., Donelli M.G., Butti G., Silvani V., et al. Concentrations of VP16 and VM26 in human brain tumors. Annals of Oncology 1991, 2(1):63-66.