Intratumoral injection of BCNU in ethanol (DTI-015) results in enhanced delivery to tumor – a pharmacokinetic study
dc.contributor.author | Moffat, Bradford A. | en_US |
dc.contributor.author | Hall, Daniel E. | en_US |
dc.contributor.author | Young, John M. | en_US |
dc.contributor.author | Desmond, Timothy J. | en_US |
dc.contributor.author | Carter, Julie | en_US |
dc.contributor.author | Pietronigro, Dennis | en_US |
dc.contributor.author | Frey, Kirk A. | en_US |
dc.contributor.author | Rehemtulla1, Alnawaz | en_US |
dc.contributor.author | Ross, Brian D. | en_US |
dc.contributor.author | Hamstra1, Daniel A. | en_US |
dc.date.accessioned | 2006-09-11T16:00:39Z | |
dc.date.available | 2006-09-11T16:00:39Z | |
dc.date.issued | 2005-07 | en_US |
dc.identifier.citation | Hamstra1, Daniel A.; Moffat, Bradford A.; Hall, Daniel E.; Young, John M.; Desmond, Timothy J.; Carter, Julie; Pietronigro, Dennis; Frey, Kirk A.; Rehemtulla1, Alnawaz; Ross, Brian D.; (2005). "Intratumoral injection of BCNU in ethanol (DTI-015) results in enhanced delivery to tumor – a pharmacokinetic study." Journal of Neuro-Oncology 73(3): 225-238. <http://hdl.handle.net/2027.42/45396> | en_US |
dc.identifier.issn | 0167-594X | en_US |
dc.identifier.issn | 1573-7373 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/45396 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=15980973&dopt=citation | en_US |
dc.description.abstract | Solvent facilitated perfusion (SFP) has been proposed as a technique to increase the delivery of chemotherapeutic agents to tumors. SFP entails direct injection of the agent into the tumor in a water-miscible organic solvent, and because the solvent moves easily through both aqueous solutions and cellular membranes it drives the penetration of the solubilized anticancer agent throughout the tumor. To test this hypothesis, we compared the pharmacokinetics (PK) of 14 C-labeled 1,3-bis-chlorethyl-1-nitrosourea (BCNU) in intra-cerebral 9L rat gliomas after intravenous (IV) infusion in 90% saline –10% ethanol or direct intratumoral (IT) injection of 14 C-BCNU in 100% ethanol (DTI-015). Treatment with DTI-015 yielded a peak radioactive count (Cmax) for the 14 C label that was 100–1000 fold higher in the tumor than in all other tissues in addition to a concentration in the tumor that was 100-fold higher than that achieved following IV infusion of 14 C-BCNU. Pathologic and auto-radiographic analysis of tissue sections following IT injection of 14 C-BCNU in ethanol into either tumor or normal rat brain revealed both an enhanced local volume of distribution and an increased concentration of BCNU delivered to tumor compared to non-tumor bearing brain. To investigate the mechanism behind the SFP of BCNU to the tumor both dynamic contrast and perfusion MRI were performed on 9L tumors before and after treatment and demonstrated a decrease in tumor perfusion following IT injection of DTI-015. Finally, initial PK of patient blood samples following administration of DTI-015 into relapsed high-grade glioma indicated a 20-fold decrease in systemic exposure to BCNU compared to IV infusion of BCNU providing further evidence for the enhanced therapeutic ratio observed for DTI-015. | en_US |
dc.format.extent | 577835 bytes | |
dc.format.extent | 3115 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Kluwer Academic Publishers; Springer | en_US |
dc.subject.other | Brain Tumor | en_US |
dc.subject.other | Medicine & Public Health | en_US |
dc.subject.other | Pharmacokinetics | en_US |
dc.subject.other | Oncology | en_US |
dc.subject.other | Animal Model | en_US |
dc.subject.other | BCNU | en_US |
dc.subject.other | MRI | en_US |
dc.title | Intratumoral injection of BCNU in ethanol (DTI-015) results in enhanced delivery to tumor – a pharmacokinetic study | en_US |
dc.type | Article | en_US |
dc.subject.hlbsecondlevel | Public Health | en_US |
dc.subject.hlbsecondlevel | Otolaryngology | en_US |
dc.subject.hlbsecondlevel | Ophthalmology | en_US |
dc.subject.hlbsecondlevel | Oncology and Hematology | en_US |
dc.subject.hlbsecondlevel | Obstetrics and Gynecology | en_US |
dc.subject.hlbsecondlevel | Neurosciences | en_US |
dc.subject.hlbsecondlevel | Internal Medicine and Specialties | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | The Departments of Radiation Oncology, The University of Michigan Medical Center, Ann Arbor, MI, USA; The Center for Molecular Imaging, The University of Michigan Medical Center, 9403 MSRB III, 1500 East Medical Center Drive, Ann Arbor, MI, 48109-0648, USA | en_US |
dc.contributor.affiliationum | Direct Therapeutics Inc., The University of Michigan Medical Center, Redwood City, CA, USA | en_US |
dc.contributor.affiliationum | The Departments of Radiology, The University of Michigan Medical Center, Ann Arbor, MI, USA; The Departments of Radiation Oncology, The University of Michigan Medical Center, Ann Arbor, MI, USA; The Center for Molecular Imaging, The University of Michigan Medical Center, 9403 MSRB III, 1500 East Medical Center Drive, Ann Arbor, MI, 48109-0648, USA | en_US |
dc.contributor.affiliationum | The Mental Health Research Institute, The University of Michigan Medical Center, Ann Arbor, MI | en_US |
dc.contributor.affiliationum | The Departments of Radiology, The University of Michigan Medical Center, Ann Arbor, MI, USA; The Departments of Biological Chemistry, The University of Michigan Medical Center, Ann Arbor, MI, USA; The Center for Molecular Imaging, The University of Michigan Medical Center, 9403 MSRB III, 1500 East Medical Center Drive, Ann Arbor, MI, 48109-0648, USA | en_US |
dc.contributor.affiliationum | The Departments of Radiology, The University of Michigan Medical Center, Ann Arbor, MI, USA; The Departments of Neurology, The University of Michigan Medical Center, Ann Arbor, MI, USA; The Mental Health Research Institute, The University of Michigan Medical Center, Ann Arbor, MI | en_US |
dc.contributor.affiliationum | Direct Therapeutics Inc., The University of Michigan Medical Center, Redwood City, CA, USA | en_US |
dc.contributor.affiliationum | Direct Therapeutics Inc., The University of Michigan Medical Center, Redwood City, CA, USA | en_US |
dc.contributor.affiliationum | The Departments of Radiology, The University of Michigan Medical Center, Ann Arbor, MI, USA; The Center for Molecular Imaging, The University of Michigan Medical Center, 9403 MSRB III, 1500 East Medical Center Drive, Ann Arbor, MI, 48109-0648, USA | en_US |
dc.contributor.affiliationum | The Departments of Radiology, The University of Michigan Medical Center, Ann Arbor, MI, USA; The Center for Molecular Imaging, The University of Michigan Medical Center, 9403 MSRB III, 1500 East Medical Center Drive, Ann Arbor, MI, 48109-0648, USA | en_US |
dc.contributor.affiliationumcampus | Ann Arbor | en_US |
dc.identifier.pmid | 15980973 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/45396/1/11060_2004_Article_5675.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1007/s11060-004-5675-2 | en_US |
dc.identifier.source | Journal of Neuro-Oncology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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