title: Predictive Value of Asphericity in Pretherapeutic [111In]DTPA-Octreotide SPECT/CT for Response to Peptide Receptor Radionuclide Therapy with [177Lu]DOTATATE.
abstract: The purpose of this study was to assess the value of the spatial heterogeneity of somatostatin receptor (SSR) volume, quantified as asphericity (ASP), and to predict response to peptide receptor radionuclide therapy (PRRT) in patients with metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN).
  
  
  
  From June 2011 to May 2013, patients suffering from GEP-NEN who underwent pretherapeutic [111In-DTPA0]octreotide scintigraphy (Octreoscan®) prior to [177Lu-DOTA0-Tyr3]octreotate ([177Lu]DOTATATE)-PRRT were enrolled in this retrospective evaluation. SSR expression in 20 NEN patients was qualitatively and quantitatively assessed using the Krenning score, the metastasis to liver uptake ratio (M/L ratio), and ASP at baseline. Response to PRRT was evaluated based on lesions, which were classified as responding lesions (RL) and non-responding lesions (NRL) after 4- and 12-month follow-ups. The values of the Krenning score, M/L ratio, and ASP for response prediction were compared by using the Mann-Whitney U test, Kruskal-Wallis test, and receiver operating characteristic (ROC) curves.
  
  
  
  Seventy-seven metastases (liver, n = 40; lymph node, n = 24; bone, n = 11; pancreas, n = 2) showed SSR expression. A higher ASP level was significantly associated with poorer response at both time points. ROC analyses revealed the highest area under the curve (AUC) for discrimination between RL and NRL for ASP after 4 months (AUC 0.97; p = 0.019) and after 12 months (AUC 0.96; p < 0.001), followed by the Krenning score (AUC 0.74; p = 0.082 and AUC 0.85; p < 0.001, respectively) and M/L ratio (AUC 0.77; p = 0.107 and AUC 0.82; p < 0.001). The optimal cutoff value for ASP was 5.12 % (sensitivity, 90 %; specificity, 93 %).
  
  
  
  Asphericity of SSR-expressing lesions in pretherapeutic single-photon emission computed tomography with integrated computed tomography (SPECT/CT) is a promising parameter for predicting response to PRRT in gastroenteropancreatic neuroendocrine neoplasms.
authors.affiliation: Department of Radiology and Nuclear Medicine, University Hospital, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wetz
authors.affiliation: Department of Radiology and Nuclear Medicine, University Hospital, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Apostolova
authors.affiliation: Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: I G
authors.initials: IG
authors.lastname: Steffen
authors.affiliation: Institute of Radiopharmaceutical Cancer Research, PET Center, Helmholtz-Zentrum Dresden-Rossendorf, P.O. Box 510119, 01314, Dresden, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Hofheinz
authors.affiliation: Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Furth
authors.affiliation: Department of Radiology and Nuclear Medicine, University Hospital, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Kupitz
authors.affiliation: Department of Nuclear Medicine, University Hospital Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Ruf
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Venerito
authors.affiliation: Department of Nephrology and Hypertension, Diabetology and Endocrinology, University Hospital, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Klose
authors.affiliation: Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. holger.amthauer@charite.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Amthauer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy*; D015282:Octreotide / Q000031:analogs & derivatives* / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D012372:ROC Curve; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D018000:Receptors, Peptide / Q000627:therapeutic use*; D000072098:Single Photon Emission Computed Tomography Computed Tomography; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: C497824:111In-octreotide, DTPA(0)-; D019275:Radiopharmaceuticals; D018000:Receptors, Peptide; D004369:Pentetic Acid; D015282:Octreotide
keywords: Asphericity; Neuroendocrine neoplasm; Peptide receptor radionuclide therapy; [111In-DTPA0]octreotide scintigraphy