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Characterization of ⁶⁸Ga-DOTA-D-Phe¹-Tyr³-Octreotide Kinetics in Patients with Meningiomas

¹ Department of Nuclear Medicine, University of Heidelberg, Heidelberg, Germany
² Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany
³ Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany
⁴ Division of Radiochemistry and Radiopharmacology, German Cancer Research Center, Heidelberg, Germany
⁵ Department of Innovative Cancer Diagnostics and Therapy, German Cancer Research Center, Heidelberg, Germany
⁶ University Hospital Basel, Basel, Switzerland

Because biopsy has a high risk of hemorrhage and the findings of CT and MRI are often ambiguous, especially at the base of the skull, additional methods for the characterization of intracranial tumors are needed. Meningiomas show high expression of the somatostatin receptor subtype 2 and thus offer the possibility of receptor-targeted imaging. We used the somatostatin analog ⁶⁸Ga-DOTA-D-Phe¹-Tyr³-octreotide (DOTA-TOC) labeled with the positron emitter ⁶⁸Ga (half-life, 68 min), obtained from a ⁶⁸Ge/⁶⁸Ga generator, for PET of these tumors. In contrast to ¹⁸F-FDG, this ligand shows high meningioma-to-background ratios. The aim was to evaluate kinetic parameters in meningiomas before radiotherapy. Methods: Dynamic PET scans (3-dimensional mode; 28 frames; ordered-subsets expectation maximization reconstruction) were acquired for 21 patients (mean age ± SD, 51 ± 13 y) before radiotherapy during the 60 min after intravenous injection of 156 ± 29 MBq of ⁶⁸Ga-DOTA-TOC. We analyzed 28 meningiomas (median grade [I] according to the system of the World Health Organization) with volumes of at least 0.5 mL (mean volume, 13.1 mL) and nasal mucosa as reference tissue, showing a slight to moderate physiologic uptake. For evaluation of the ⁶⁸Ga-DOTA-TOC kinetics, the vascular fraction (vB) and the rate constants (k1, k2, k3, and k4 [1/min]) were computed using a 2-tissue-compartment model. Furthermore, receptor binding (RB) (k1 – k1 x k2) and the ratios k1/k2 and k3/k4 were calculated. Results: Significant differences (P < 0.05; t test) between meningiomas and the reference tissue were found for the mean standardized uptake value (10.5 vs.1.3), vB (0.42 vs. 0.11), k2 (0.12 vs. 0.56), k3 (0.024 vs. 0.060), k4 (0.004 vs. 0.080), and RB (0.49 vs. 0.13). Although there was no significant difference for k1 (0.54 vs. 0.40), the ratios k1/k2 (4.50 vs. 0.71) and k3/k4 (6.00 vs. 0.75) were markedly greater in meningiomas than in reference tissue. Conclusion: The high uptake of ⁶⁸Ga-DOTA-TOC in meningiomas can be explained by the high values for vB and by the remarkably low values for k2 and k4, leading to significantly greater k1/k2 and k3/k4 ratios and RB in meningiomas than in reference tissue. Thus, pharmacokinetic modeling offers a more detailed analysis of biologic properties of meningiomas. In further studies, these data might serve as a basis for monitoring the somatostatin receptors of meningiomas after radiotherapy.

Key Words: somatostatin receptors • ⁶⁸Ga-DOTA-TOC • PET • kinetic modeling • meningioma

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