title: Peptide receptor radionuclide therapy of neuroendocrine tumors with (90)Y-DOTATOC: is treatment response predictable by pre-therapeutic uptake of (68)Ga-DOTATOC?
abstract: OBJECTIVE
  PET with (68)Ga-DOTATOC allows for imaging and quantitative assessment of somatostatin receptor expression in neuroendocrine tumors (NET). The aim of this retrospective study was to analyze whether pre-therapeutic (68)Ga-DOTATOC PET/CT is able to predict response to Peptide Receptor Radionuclide Therapy (PRRT).
  
  
  METHODS
  Forty patients with advanced stage NET were treated with a fixed dose of (90)Y-DOTATOC (5550 or 3700MBq). Prior to PRRT, each patient received (68)Ga-DOTATOC PET/CT. Treatment results were evaluated after 3months by CT, tumor marker levels and clinical course and correlated with (68)Ga-DOTATOC uptake (SUVmax) and the assumed uptake of (90)Y-DOTATOC in tumor manifestations (MBq/g). ROC analysis and pairwise comparison of area under the curve (AUC) were performed with pre-treatment uptake of (68)Ga-DOTATOC, assumed uptake of (90)Y-DOTATOC and treatment activity alone and in relation to body weight as continuous variables, and response/no response as classification variable.
  
  
  RESULTS
  According to conventional criteria (tumor shrinkage, decrease of tumor markers, improved or stable clinical condition), 20 patients were classified as responders, 16 as non-responders and in four patients findings were equivocal. Using a SUV more than 17.9 as cut-off for favorable outcome, PET was able to predict treatment response of all responders and 15 out of 16 non-responders. All four patients with equivocal findings showed SUV less than or equal to 17.9 and soon experienced tumor progression. The assumed uptake of (90)Y-DOTATOC in tumor manifestations using a cut-off more than 1.26MBq/g as predictor of response was able to correctly classify 19 out of 20 responders, and 14 out of 16 non-responders. In all patients with equivocal findings, the assumed uptake of (90)Y-DOTATOC was below 1.26MBq/g.
  
  
  CONCLUSIONS
  Pre-therapeutic (68)Ga-DOTATOC tumor uptake as well as assumed uptake of (90)Y-DOTATOC are strongly associated with the results of subsequent PRRT. The defined cut-off values should be confirmed by prospective studies and may then provide the rationale for individual dosing and selecting patients with high likelihood of favorable treatment outcome.
authors.affiliation: Département d'Imagerie Médicale, Hôpital neuchâtelois, Maladière 45, 2000 Neuchâtel, Switzerland; Department of Nuclear Medicine, Tübingen University Hospital, Otfried-Müller-Strasse 14, 72076 Tübingen, Germany. Electronic address: mehmet-ozer.oksuz@ne.ch.
authors.forename: M Ö
authors.initials: MÖ
authors.lastname: Öksüz
authors.affiliation: Department of Radiology and Nuclear Medicine, Basel University Hospital, Petersgraben 4, 4031 Basel, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Winter
authors.affiliation: Department of Radiology, Tübingen University Hospital, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Pfannenberg
authors.affiliation: Department of Radiopharmacy, Tübingen University Hospital, Röntgenweg 15, 72076 Tübingen, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Reischl
authors.affiliation: Deutsches Diabetes-Zentrum (DDZ), Leibniz-Zentrum für Diabetes-Forschung an der Heinrich-Heine-Universität Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Müssig
authors.affiliation: Department of Nuclear Medicine, Tübingen University Hospital, Otfried-Müller-Strasse 14, 72076 Tübingen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Bares
authors.affiliation: Department of Nuclear Medicine, Tübingen University Hospital, Otfried-Müller-Strasse 14, 72076 Tübingen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Dittmann
mesh_terms: D000328:Adult; D000368:Aged; D003299:Cooperative Behavior; D057510:Endovascular Procedures / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D033183:Interdisciplinary Communication; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D009942:Organometallic Compounds; D049268:Positron-Emission Tomography / Q000379:methods*; D011237:Predictive Value of Tests; D017481:Receptors, Somatostatin / Q000032:analysis*; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D009942:Organometallic Compounds; D017481:Receptors, Somatostatin; C513399:gallium Ga 68 dotatate
keywords: (68)Ga-DOTATOC; (90)Y-DOTATOC; Neuroendocrine tumor; PET/CT; PRRT