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Locoregional Regulatory Peptide Receptor Targeting with the Diffusible Somatostatin Analogue ⁹⁰Y-Labeled DOTA⁰-D-Phe¹-Tyr³-octreotide (DOTATOC): A Pilot Study in Human Gliomas¹

Neurosurgical Clinic [A. M., O. H., M. W., O. G.], Institute and Clinic of Nuclear Medicine [A. O., J. M-B.], Radiological Chemistry Unit [P. S., E. J., H. R. M.], and Neuroradiology [P. F.], University Hospital Basel, CH-4031 Basel, and Institute of Pathology, University of Berne, CH-3010 Berne [J-C. R.], Switzerland

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 ¹¹¹In-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.

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