Locoregional regulatory peptide receptor targeting with the diffusible somatostatin analogue 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC): a pilot study in human gliomas
| Autor: | A, Merlo, O, Hausmann, M, Wasner, P, Steiner, A, Otte, E, Jermann, P, Freitag, J C, Reubi, J, Müller-Brand, O, Gratzl, H R, Mäcke |
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| Rok vydání: | 1999 |
| Předmět: |
Adult
Male Radioisotopes Brain Neoplasms Oligodendroglioma Brain Edema Pilot Projects Radiotherapy Dosage Glioma Astrocytoma Injections Intralesional Middle Aged Octreotide Binding Competitive Neoplasm Proteins Diffusion Stereotaxic Techniques Disease Progression Humans Female Tissue Distribution Receptors Somatostatin Radiopharmaceuticals Ytterbium Glioblastoma |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 5(5) |
| ISSN: | 1078-0432 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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