title: Intracarotid infusion of RMP-7, a bradykinin analog, and transport of gallium-68 ethylenediamine tetraacetic acid into human gliomas.
abstract: The bradykinin analog, RMP-7, was investigated for its ability to increase selectively the transport of 68Ga ethylenediamine tetraacetic acid (EDTA) into recurrent malignant gliomas in nine patients. For each patient, two position emission tomography (PET) studies (one with and one without RMP-7) were performed. For studies with RMP-7, 10 to 300 ng/kg of the compound was infused into the supraophthalmic carotid artery over 15 minutes. In each PET study, a sequence of PET scans was initiated simultaneously with an intravenous bolus of 68Ga EDTA (5-10 mCi). Arterial samples were taken to provide the input function. All PET scans were coregistered to the magnetic resonance (MR) images of the patient. Regions of interest were defined for tumor and normal tissue regions on MR images and were copied to the coregistered PET dynamic images to provide brain tissue-time activity curves. The constant (Ki) for the transport of gallium-68 from plasma to brain tissue was determined using a simple compartmental model. Intracarotid infusion of RMP-7 significantly increased transport into tumor regions with an average increase of 46 +/- 42% (mean +/- standard deviation, p < 0.05). Permeability in normal tissue regions was not significantly increased. Tumors in three of six patients treated with 300 ng/kg RMP-7 and carboplatin had at least a 50% reduction in tumor volume as measured by MR imaging. Intracarotid infusion of RMP-7 is a novel technique for selective delivery of antitumor compounds into brain tumors.
authors.affiliation: Jonsson Comprehensive Cancer Center, Department of Neurology, University of California, Los Angeles Medical Center, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Black
authors.forename: T
authors.initials: T
authors.lastname: Cloughesy
authors.forename: S C
authors.initials: SC
authors.lastname: Huang
authors.forename: Y P
authors.initials: YP
authors.lastname: Gobin
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: J
authors.initials: J
authors.lastname: Grous
authors.forename: G
authors.initials: G
authors.lastname: Nelson
authors.forename: K
authors.initials: K
authors.lastname: Farahani
authors.forename: C K
authors.initials: CK
authors.lastname: Hoh
authors.forename: M
authors.initials: M
authors.lastname: Phelps
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001692:Biological Transport / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D016190:Carboplatin / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004492:Edetic Acid / Q000493:pharmacokinetics*; D005260:Female; D005710:Gallium Radioisotopes; D005910:Glioma / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D007269:Injections, Intra-Arterial; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D014055:Tomography, Emission-Computed
chemical_list: D000970:Antineoplastic Agents; D005710:Gallium Radioisotopes; C089876:RMP 7; D004492:Edetic Acid; D016190:Carboplatin; D001920:Bradykinin