title: Characterization of 68Ga-DOTA-D-Phe1-Tyr3-octreotide kinetics in patients with meningiomas.
abstract: 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 (68)Ga-DOTA-d-Phe(1)-Tyr(3)-octreotide (DOTA-TOC) labeled with the positron emitter (68)Ga (half-life, 68 min), obtained from a (68)Ge/(68)Ga generator, for PET of these tumors. In contrast to (18)F-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 (68)Ga-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 (68)Ga-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.
  
  
  CONCLUSIONS
  The high uptake of (68)Ga-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.
authors.affiliation: Department of Nuclear Medicine, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. Marcus.Heinze@med.uni-heidelberg.de
authors.forename: Marcus
authors.initials: M
authors.lastname: Henze
authors.forename: Antonia
authors.initials: A
authors.lastname: Dimitrakopoulou-Strauss
authors.forename: Stefanie
authors.initials: S
authors.lastname: Milker-Zabel
authors.forename: Jochen
authors.initials: J
authors.lastname: Schuhmacher
authors.forename: Ludwig G
authors.initials: LG
authors.lastname: Strauss
authors.forename: Josef
authors.initials: J
authors.lastname: Doll
authors.forename: Helmut R
authors.initials: HR
authors.lastname: Mäcke
authors.forename: Michael
authors.initials: M
authors.lastname: Eisenhut
authors.forename: Jürgen
authors.initials: J
authors.lastname: Debus
authors.forename: Uwe
authors.initials: U
authors.lastname: Haberkorn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D005710:Gallium Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D007700:Kinetics; D008297:Male; D008577:Meningeal Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008579:Meningioma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D015282:Octreotide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics
chemical_list: D005710:Gallium Radioisotopes; D019275:Radiopharmaceuticals; D015282:Octreotide; C106246:Edotreotide