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

高级别胶质瘤中的生长抑素受体亚型 2:PET/CT 与 (68)Ga-DOTA-肽、与预后标志物的相关性以及对靶向放射治疗的影响

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作者:Aida Kiviniemi, Maria Gardberg, Janek Frantzén, Marko Pesola, Ville Vuorinen, Riitta Parkkola, Tuula Tolvanen, Sami Suilamo, Jarkko Johansson, Pauliina Luoto, Jukka Kemppainen, Anne Roivainen, Heikki Minn

Background

High-grade gliomas (HGGs) express somatostatin receptors (SSTR), rendering them candidates for peptide receptor radionuclide therapy (PRRT). Our

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.

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.

Trial registration

ClinicalTrials.gov NCT01460706.

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