Alexander Natasha, Marrano Paula, Thorner Paul, Naranjo Arlene, Van Ryn Collin, Martinez Daniel, Batra Vandana, Zhang Libo, Irwin Meredith S, Baruchel Sylvain
Departments of Pediatrics, Division of Hematology/Oncology.
Departments of Pediatrics.
J Pediatr Hematol Oncol. 2019 Apr;41(3):222-227. doi: 10.1097/MPH.0000000000001326.
Alternative radiolabeled, targeted agents are being investigated for children with relapsed neuroblastoma (NB) who do not respond to I-metaiodobenzylguanidine (MIBG) therapy. (DOTA-Tyr)-octreotate targets somatostatin receptors (SSTRs), particularly SSTR2, which are expressed on NB cells. We investigated SSTR2 expression in NB tumors (36 high-risk [HR]; 33 non-HR patients) and correlated SSTR2 levels with clinical features, norepinephrine transporter (NET) expression, and MIBG avidity. SSTR2 and NET immunohistochemistry scores (0 to 3) were calculated on biopsies using digital image analysis based on staining intensity and distribution. Clinical data were correlated with SSTR2 expression. Median SSTR2 score for 69 patients was 1.31 (0.26 to 2.55). Non-HR NB was associated with a higher SSTR2 score (P=0.032). The SSTR2 expression did not correlate with age, International Neuroblastoma Staging System (INSS) stage, MYCN amplification and histology. Higher SSTR2 scores were observed in MIBG-avid versus MIBG-nonavid NB. SSTR2 score was not significantly associated with NET score (r=-0.062, P=0.62). Twenty-six patients who relapsed or progressed had a median SSTR2 score of 1.33 (0.26 to 2.55). Patients with NB including relapsed or progressive disease showed SSTR2 expression at diagnosis, suggesting they could be candidates for radiolabeled-DOTA-conjugated peptide imaging or therapy.
对于复发的神经母细胞瘤(NB)且对碘代间位碘苄胍(MIBG)治疗无反应的儿童,正在研究替代性放射性标记的靶向药物。(DOTA-酪氨酸)-奥曲肽靶向生长抑素受体(SSTRs),特别是在NB细胞上表达的SSTR2。我们研究了NB肿瘤(36例高危[HR];33例非HR患者)中SSTR2的表达,并将SSTR2水平与临床特征、去甲肾上腺素转运体(NET)表达和MIBG亲和力相关联。使用基于染色强度和分布的数字图像分析,对活检组织计算SSTR2和NET免疫组化评分(0至3)。将临床数据与SSTR2表达相关联。69例患者的SSTR2评分中位数为1.31(0.26至2.55)。非HR NB与较高的SSTR2评分相关(P = 0.032)。SSTR2表达与年龄、国际神经母细胞瘤分期系统(INSS)分期、MYCN扩增和组织学无关。在MIBG摄取阳性与MIBG摄取阴性的NB中观察到较高的SSTR2评分。SSTR2评分与NET评分无显著相关性(r = -0.062,P = 0.62)。26例复发或进展的患者SSTR2评分中位数为1.33(0.26至2.55)。包括复发或进展性疾病的NB患者在诊断时显示SSTR2表达,表明他们可能是放射性标记的DOTA偶联肽成像或治疗的候选者。