A surgical technique for safely placing a drug delivery catheter into the pons of primates: Preliminary results of carboplatin infusion

Phillip B. Storm, Richard E. Clatterbuck, Ya J. Liu, Randolph M. Johnson, Edward M. Gillis, Michael Guarnieri, Benjamin S. Carson, Richard D. Penn, Dennis Groothuis, Jeffrey N. Bruce

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: We sought to develop a neurosurgical procedure to access the pons with a drug delivery device for chronic therapy and collect preliminary data on the toxicity of direct infusions of carboplatin in primates. METHODS: We made midline incisions on five cynomolgus monkeys, identified the inion, made a burr hole 2.5 cm below the inion, and inserted a catheter through the cerebellum into the roof of the pons. Pumps that infused saline for 90 days or carboplatin solutions for 30 to 35 days at 10 μl/d were placed subcutaneously in the low cervical/high thoracic region. Monkeys were assessed by computed tomography and magnetic resonance imaging, laboratory studies, daily neurological observation, postmortem examinations, and histopathology. RESULTS: Monkeys infused with saline and 82 μg of carboplatin remained neurologically intact throughout the infusion periods. Sedal imaging showed that the catheter tip was in the pons and revealed no evidence of hemorrhage, edema, or migration. Two monkeys infused with up to 850 μg of carboplatin showed hyperintense magnetic resonance imaging signals at Days 15 and 18 and neurological deficits at approximately Week 3. Platinum levels greater than 10 ng/mg tissue were detected over a distance of 1 cm in tissue slices. Histopathology demonstrated significant tissue necrosis around the tip of the catheter. CONCLUSION: The pons of monkeys is safely accessed with a catheter for drug delivery by using a posterior midline approach. Clinical observations, radiographic imaging, and laboratory tests of animals infused with saline for 3 months or 0.26 mg/ml of carboplatin for 1 month were unremarkable. Neurotoxicity was seen with dose levels of 2.6 mg/ml of drug for 1 month. This procedure offers opportunities for examining the toxicity of brainstem antitumor therapy in primates.

Original languageEnglish (US)
Pages (from-to)1169-1177
Number of pages9
JournalNeurosurgery
Volume52
Issue number5
StatePublished - May 1 2003

Keywords

  • Brainstem
  • Carboplatin
  • Catheters
  • Infusion pump
  • Local delivery
  • Pontine glioma

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Fingerprint Dive into the research topics of 'A surgical technique for safely placing a drug delivery catheter into the pons of primates: Preliminary results of carboplatin infusion'. Together they form a unique fingerprint.

  • Cite this

    Storm, P. B., Clatterbuck, R. E., Liu, Y. J., Johnson, R. M., Gillis, E. M., Guarnieri, M., Carson, B. S., Penn, R. D., Groothuis, D., & Bruce, J. N. (2003). A surgical technique for safely placing a drug delivery catheter into the pons of primates: Preliminary results of carboplatin infusion. Neurosurgery, 52(5), 1169-1177.