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01.01.2016 | Short Communication

Enhanced brain distribution of carboplatin in a primate model after blood–brain barrier disruption using an implantable ultrasound device

verfasst von: Lauriane Goldwirt, Michael Canney, Catherine Horodyckid, Joel Poupon, Samia Mourah, Alexandre Vignot, Jean-Yves Chapelon, Alexandre Carpentier

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 1/2016

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Abstract

Purpose

Glioblastoma is both the most common and aggressive primary brain tumor in adults. Carboplatin chemotherapy has shown only modest efficacy in progressive high-grade gliomas. The limited clinical efficacy of carboplatin may be due to its low concentration in tissue when the drug is delivered intravenously. The aim of this study was to assess whether the tissue concentration of intravenously administered carboplatin could be enhanced by ultrasound-induced blood–brain disruption in a primate model.

Methods

Carboplatin was administered intravenously for 60 min to a single primate following blood–brain barrier opening induced by an implantable ultrasound device. Blood and brain samples were collected after animal killing, which occurred 60 min after the end of carboplatin administration. Platinum quantification in ultrafiltrate plasma and brain samples was performed using inductively coupled plasma mass spectrometry.

Results

The brain concentration of platinum was highly enhanced (5.2×) in the 3.9 cm³ region sonicated by the US beam, with a higher concentration in more vascularized anatomical structures. At 5 and 10 mm from the US beam axis, platinum concentrations were slightly enhanced (2.2× and 1.3× respectively).

Conclusions

This study demonstrates that BBB opening using an implantable ultrasound transducer enhances the brain distribution of carboplatin in a loco-regional manner. Such a treatment approach is of significant interest for the treatment of primary brain tumors and is under current evaluation in a phase 1 clinical trial (NCT02253212).

Jansen M, de Witt Hamer PC, Witmer AN, Troost D, van Noorden CJF (2004) Current perspectives on antiangiogenesis strategies in the treatment of malignant gliomas. Brain Res Rev 45(3):143–163PubMedCrossRef

Steiner H-H, Karcher S, Mueller MM, Nalbantis E, Kunze S, Herold-Mende C (2004) Autocrine pathways of the vascular endothelial growth factor (VEGF) in glioblastoma multiforme: clinical relevance of radiation-induced increase of VEGF levels. J Neurooncol 66(1):129–138PubMedCrossRef

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, Belanger K, Brandes AA, Marosi C, Bogdahn U, Jr Curschmann, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996PubMedCrossRef

Warnick R, Prados M, Mack E, Chandler K, Doz F, Rabbitt J, Malec M (1994) A phase II study of intravenous carboplatin for the treatment of recurrent gliomas. J Neurooncol 19(1):69–74PubMedCrossRef

Prados MD, Warnick RE, Mack EE, Chandler KL, Rabbitt J, Page M, Malec M (1996) Intravenous carboplatin for recurrent gliomas. A dose-escalating phase II trial. Am J Clin Oncol 19(6):609–612PubMedCrossRef

Murray LJ, Bridgewater CH, Levy D (2011) Carboplatin chemotherapy in patients with recurrent high-grade glioma. Clinical Oncology 23(1):55–61PubMedCrossRef

Roci E, Cakani B, Brace G, Bushati T, Rroji A, Petrela M, Kaloshi G (2014) Platinum-based chemotherapy in recurrent high-grade glioma patients: retrospective study. Med Arch (Sarajevo, Bosnia and Herzegovina) 68(2):140–143

Pitz M, Desai A, Grossman S, Blakeley J (2011) Tissue concentration of systemically administered antineoplastic agents in human brain tumors. J Neurooncol 104(3):629–638PubMedPubMedCentralCrossRef

Jacobs S, McCully CL, Murphy RF, Bacher J, Balis FM, Fox E (2010) Extracellular fluid concentrations of cisplatin, carboplatin, and oxaliplatin in brain, muscle, and blood measured using microdialysis in nonhuman primates. Cancer Chemother Pharmacol 65(5):817–824PubMedCrossRef

10.

Fortin D, Morin P-A, Belzile F, Mathieu D, Paré F-M (2014) Intra-arterial carboplatin as a salvage strategy in the treatment of recurrent glioblastoma multiforme. J Neurooncol 119(2):397–403PubMedCrossRef

11.

White E, Bienemann A, Taylor H, Hopkins K, Cameron A, Gill S (2012) A phase I trial of carboplatin administered by convection-enhanced delivery to patients with recurrent/progressive glioblastoma multiforme. Contemp Clin Trials 33(2):320–331PubMedCrossRef

12.

Yang W, Huo T, Barth RF, Gupta N, Weldon M, Grecula JC, Ross BD, Hoff BA, Chou TC, Rousseau J, Elleaume H (2011) Convection enhanced delivery of carboplatin in combination with radiotherapy for the treatment of brain tumors. J Neurooncol 101(3):379–390PubMedPubMedCentralCrossRef

13.

Doolittle ND, Miner ME, Hall WA, Siegal T, Hanson EJ, Osztie E, McAllister LD, Bubalo JS, Kraemer DF, Fortin D, Nixon R, Muldoon LL, Neuwelt EA (2000) 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 88(3):637–647PubMedCrossRef

14.

Williams PC, Henner WD, Roman-Goldstein S, Dahlborg SA, Brummett RE, Tableman M, Dana BW, Neuwelt EA (1995) Toxicity and efficacy of carboplatin and etoposide in conjunction with disruption of the blood–brain tumor barrier in the treatment of intracranial neoplasms. Neurosurgery 37(1):17–27 (discussion 27–18) PubMedCrossRef

15.

Hynynen K, McDannold N, Vykhodtseva N, Jolesz FA (2001) Noninvasive MR imaging-guided focal opening of the blood–brain barrier in rabbits. Radiology 220(3):640–646PubMedCrossRef

16.

Beccaria K, Canney M, Goldwirt L, Fernandez C, Adam C, Piquet J, Autret G, Clement O, Lafon C, Chapelon JY, Carpentier A (2013) Opening of the blood–brain barrier with an unfocused ultrasound device in rabbits. J Neurosurg 119(4):887–898PubMedCrossRef

17.

Carpentier A, Canney M, Horodyckid C, Leclercq D, Vignot A, Beccaria K, Boisgard R, Goldwirt L, Reina V, Lafon C, Chapelon J, Capelle L, Dehais C, Cornu P, Delattre J, Idbaih A (2014) Ouverture de la barrière hémato-encéphalique par un dispositif ultrasonore implantable : résultats pré-cliniques sur primates et résultats préliminaires de l’essai clinique SonoCloud de phase I/Iia. NeuroChirurgie 60(6):329. doi:10.1016/j.neuchi.2014.10.023 CrossRef

18.

Beccaria K, Canney M, Goldwirt L, Fernandez C, Piquet J, Perier MC, Lafon C, Chapelon JY, Carpentier A (2015) Ultrasound-induced opening of the blood–brain barrier to enhance temozolomide and irinotecan delivery: an experimental study in rabbits. J Neurosurg. doi:10.3171/2015.4.jns142893 PubMed

19.

Ito H, Yamaguchi H, Fujikawa A, Shiida N, Tanaka N, Ogura J, Kobayashi M, Yamada T, Mano N, Iseki K (2013) Quantification of intact carboplatin in human plasma ultrafiltrates using hydrophilic interaction liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study. J Chromatogr B Anal Technol Biomed Life Sci 917–918:18–23CrossRef

20.

Storm PB, Clatterbuck RE, Liu YJ, Johnson RM, Gillis EM, Guarnieri M, Carson BSS (2003) A Surgical technique for safely placing a drug delivery catheter into the pons of primates: preliminary results of carboplatin infusion. Neurosurgery 52(5):1169–1177PubMedCrossRef

21.

Arshad A, Yang B, Bienemann AS, Barua NU, Wyatt MJ, Woolley M, Johnson DE, Edler KJ, Gill SS (2015) Convection-enhanced delivery of carboplatin PLGA nanoparticles for the treatment of glioblastoma. PLoS One 10(7):e0132266. doi:10.1371/journal.pone.0132266 PubMedPubMedCentralCrossRef

22.

Barua NU, Hopkins K, Woolley M, O’Sullivan S, Harrison R, Edwards RJ, Bienemann AS, Wyatt MJ, Arshad A, Gill SS (2015) A novel implantable catheter system with transcutaneous port for intermittent convection-enhanced delivery of carboplatin for recurrent glioblastoma. Drug Deliv [Epub ahead of print]. doi:10.3109/10717544.2014.908248

23.

Carpentier A, Canney M, Vignot A, Horodyckid C, Goldwirt L, Leclercq D, Delattre JY, Chapelon JY, Idbaih A Temporary disruption of the blood–brain barrier using an implantable ultrasound system for recurrent glioblastoma patients under IV carboplatin chemotherapy: initial phase 1/2a clinical trial observations. In: Current and future applications of focused ultrasound 2014. 4th International Symposium, Washington, DC, USA, 2014. J Ther Ultrasound 2015, p O14

Titel: Enhanced brain distribution of carboplatin in a primate model after blood–brain barrier disruption using an implantable ultrasound device
verfasst von: Lauriane Goldwirt
Michael Canney
Catherine Horodyckid
Joel Poupon
Samia Mourah
Alexandre Vignot
Jean-Yves Chapelon
Alexandre Carpentier
Publikationsdatum: 01.01.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 1/2016
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-015-2930-5

Springer Medizin

Enhanced brain distribution of carboplatin in a primate model after blood–brain barrier disruption using an implantable ultrasound device