title: Somatostatin receptor subtype 2 in high-grade gliomas: PET/CT with (68)Ga-DOTA-peptides, correlation to prognostic markers, and implications for targeted radiotherapy.
abstract: BACKGROUND
  High-grade gliomas (HGGs) express somatostatin receptors (SSTR), rendering them candidates for peptide receptor radionuclide therapy (PRRT). Our purpose was to evaluate the potential of (68)Ga-DOTA-1-Nal(3)-octreotide ((68)Ga-DOTANOC) or (68)Ga-DOTA-Tyr(3)-octreotide ((68)Ga-DOTATOC) to target SSTR subtype 2 (SSTR2) in HGGs, and to study the association between SSTR2 expression and established biomarkers.
  
  
  METHODS
  Twenty-seven patients (mean age 52 years) with primary or recurrent HGG prospectively underwent (68)Ga-DOTA-peptide positron emission tomography/computed tomography (PET/CT) before resection. Maximum standardized uptake values (SUVmax) and receptor binding potential (BP) were calculated on PET/CT and disruption of blood-brain barrier (BBB) from contrast-enhanced T1-weighted magnetic resonance imaging (MRI-T1-Gad). Tumor volume concordance between PET and MRI-T1-Gad was assessed by Dice similarity coefficient (DC) and correlation by Spearman's rank. Immunohistochemically determined SSTR2 status was compared to receptor imaging findings, prognostic biomarkers, and survival with Kruskal-Wallis, Pearson chi-square, and multivariate Cox regression, respectively.
  
  
  RESULTS
  All 19 HGGs with disrupted BBB demonstrated tracer uptake. Tumor SUVmax (2.25 ± 1.33) correlated with MRI-T1-Gad (r = 0.713, P = 0.001) although DC 0.41 ± 0.19 suggested limited concordance. SSTR2 immunohistochemistry was regarded as positive in nine HGGs (32%) but no correlation with SUVmax or BP was found. By contrast, SSTR2 expression was associated with IDH1 mutation (P = 0.007), oligodendroglioma component (P = 0.010), lower grade (P = 0.005), absence of EGFR amplification (P = 0.021), and longer progression-free survival (HR 0.161, CI 0.037 to 0.704, P = 0.015).
  
  
  CONCLUSIONS
  In HGGs, uptake of (68)Ga-DOTA-peptides is associated with disrupted BBB and cannot be predicted by SSTR2 immunohistochemistry. Thus, PET/CT shows limited value to detect HGGs suitable for PRRT. However, high SSTR2 expression portends favorable outcome along with established biomarkers such as IDH1 mutation.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01460706.
authors.affiliation: Turku PET Centre, Turku University Hospital, University of Turku, Kiinamyllynkatu 4-8, 20521 Turku, Finland ; Department of Radiology, Medical Imaging Centre of Southwest Finland, Turku University Hospital, Kiinamyllynkatu 4-8, 20521 Turku, Finland.
authors.forename: Aida
authors.initials: A
authors.lastname: Kiviniemi
authors.affiliation: Department of Pathology, Turku University Hospital, Kiinamyllynkatu 4-8, 20521 Turku, Finland.
authors.forename: Maria
authors.initials: M
authors.lastname: Gardberg
authors.affiliation: Department of Neurosurgery, Turku University Hospital, Hämeentie 11, 20521 Turku, Finland.
authors.forename: Janek
authors.initials: J
authors.lastname: Frantzén
authors.affiliation: Turku PET Centre, Turku University Hospital, University of Turku, Kiinamyllynkatu 4-8, 20521 Turku, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Pesola
authors.affiliation: Department of Neurosurgery, Turku University Hospital, Hämeentie 11, 20521 Turku, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Vuorinen
authors.affiliation: Department of Radiology, Medical Imaging Centre of Southwest Finland, Turku University Hospital, Kiinamyllynkatu 4-8, 20521 Turku, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Parkkola
authors.affiliation: Turku PET Centre, Turku University Hospital, University of Turku, Kiinamyllynkatu 4-8, 20521 Turku, Finland.
authors.forename: Tuula
authors.initials: T
authors.lastname: Tolvanen
authors.affiliation: Department of Oncology and Radiotherapy, Turku University Hospital, Hämeentie 11, 20521 Turku, Finland.
authors.forename: Sami
authors.initials: S
authors.lastname: Suilamo
authors.affiliation: Turku PET Centre, Turku University Hospital, University of Turku, Kiinamyllynkatu 4-8, 20521 Turku, Finland.
authors.forename: Jarkko
authors.initials: J
authors.lastname: Johansson
authors.affiliation: Turku PET Centre, Turku University Hospital, University of Turku, Kiinamyllynkatu 4-8, 20521 Turku, Finland.
authors.forename: Pauliina
authors.initials: P
authors.lastname: Luoto
authors.affiliation: Turku PET Centre, Turku University Hospital, University of Turku, Kiinamyllynkatu 4-8, 20521 Turku, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Kemppainen
authors.affiliation: Turku PET Centre, Turku University Hospital, University of Turku, Kiinamyllynkatu 4-8, 20521 Turku, Finland ; Turku Center for Disease Modeling, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Roivainen
authors.affiliation: Department of Oncology and Radiotherapy, Turku University Hospital, Hämeentie 11, 20521 Turku, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Minn
keywords: 68Ga-DOTANOC; High-grade glioma; IDH1 mutation; PET/CT; Somatostatin receptor