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.