Locoregional Regulatory Peptide Receptor Targeting with the Diffusible Somatostatin Analogue Y-Labeled DOTA-D-Phe-Tyr-octreotide (DOTATOC): A Pilot Study in Human Gliomas

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 Y-labeled DOTA-D-Phe-Tyr-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 I-[Tyr]-octreotide in tumor tissue sections. Diagnostic In-labeled DOTATOC-scintigraphy following local injection displayed homogeneous to nodular intratumoral vector distribution. The cumulative activity of regionally injected peptide-bound Y amounted to 370-3300 MBq, which is equivalent to an effective dose range between 60 6 15 and 550 6 110 Gy. Activity was injected in one to four fractions according to tumor volumes; 1110 MBq of Y-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.