title: Locoregional regulatory peptide receptor targeting with the diffusible somatostatin analogue 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC): a pilot study in human gliomas.
abstract: Human gliomas, especially of low-grade type, have been shown to express high-affinity somatostatin receptor type 2 (J-C. Reubi et al., Am. J. Pathol, 134: 337-344, 1989). We enrolled seven low-grade and four anaplastic glioma patients in a pilot study using the diffusible peptidic vector 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) for receptor targeting. The radiopharmakon was locoregionally injected into a stereotactically inserted Port-a-cath. DOTATOC competes specifically with somatostatin binding to somatostatin receptor type 2 in the low nanomolar range as shown by a displacement curve of 125I-[Tyr3]-octreotide in tumor tissue sections. Diagnostic (111)In-labeled DOTATOC-scintigraphy following local injection displayed homogeneous to nodular intratumoral vector distribution. The cumulative activity of regionally injected peptide-bound 90Y amounted to 370-3300 MBq, which is equivalent to an effective dose range between 60 +/- 15 and 550 +/- 110 Gy. Activity was injected in one to four fractions according to tumor volumes; 1110 MBq of 90Y-labeled DOTATOC was the maximum activity per single injection. We obtained six disease stabilizations and shrinking of a cystic low-grade astrocytoma component. The only toxicity observed was secondary perifocal edema. The activity:dose ratio (MBq:Gy) represents a measure for the stability of peptide retention in receptor-positive tissue and might predict the clinical course. We conclude that SR-positive human gliomas, especially of low-grade type, can be successfully targeted by intratumoral injection of the metabolically stable small regulatory peptide DOTATOC.
authors.affiliation: Neurosurgical Clinic, University Hospital Basel, Switzerland. amerlo@uhbs.ch
authors.forename: A
authors.initials: A
authors.lastname: Merlo
authors.forename: O
authors.initials: O
authors.lastname: Hausmann
authors.forename: M
authors.initials: M
authors.lastname: Wasner
authors.forename: P
authors.initials: P
authors.lastname: Steiner
authors.forename: A
authors.initials: A
authors.lastname: Otte
authors.forename: E
authors.initials: E
authors.lastname: Jermann
authors.forename: P
authors.initials: P
authors.lastname: Freitag
authors.forename: J C
authors.initials: JC
authors.lastname: Reubi
authors.forename: J
authors.initials: J
authors.lastname: Müller-Brand
authors.forename: O
authors.initials: O
authors.lastname: Gratzl
authors.forename: H R
authors.initials: HR
authors.lastname: Mäcke
mesh_terms: D000328:Adult; D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D001667:Binding, Competitive; D001929:Brain Edema / Q000139:chemically induced; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D004058:Diffusion; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D005910:Glioma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D015552:Injections, Intralesional; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D015282:Octreotide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009837:Oligodendroglioma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D010865:Pilot Projects; D011868:Radioisotopes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D013238:Stereotaxic Techniques; D014018:Tissue Distribution; D015018:Ytterbium / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D009363:Neoplasm Proteins; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; C093733:somatostatin receptor 2; D015018:Ytterbium; D015282:Octreotide; C106246:Edotreotide