Somatostatin receptor subtype 2 in high-grade gliomas: PET/CT with 68Ga-DOTA-peptides, correlation to prognostic markers, and implications for targeted radiotherapy

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 Ga-68-DOTA-1-Nal(3)-octreotide (Ga-68-DOTANOC) or Ga-68-DOTA-Tyr(3)-octreotide (Ga-68-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 Ga-68-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 Ga-68-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.