Maratta Maria Grazia, Al-Toubah Taymeyah, Montilla-Soler Jaime, Pelle Eleonora, Haider Mintallah, El-Haddad Ghassan, Strosberg Jonathan
Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Cancers (Basel). 2025 Jun 11;17(12):1937. doi: 10.3390/cancers17121937.
There is limited data on somatostatin receptor (SSTR) expression of metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) using modern imaging techniques and stratifying by primary site and tumor grade (G). Understanding patterns of SSTR expression and tumor heterogeneity is essential when determining the relevance of cold and radiolabeled somatostatin analog treatments. A single-institutional retrospective analysis of metastatic well-differentiated G1-3 GEP-NET patients who underwent Gallium-68 ([Ga])-DOTATATE or Copper-64 ([Cu])-DOTATATE positron emission tomography (PET) imaging from September 2016 to June 2024 was performed. A total of 1192 patients were considered eligible for this study. Among them, 26 (2.2%) were completely negative on SSTR PET/computed tomography (CT), and 27 (2.3%) had weak uptake (less or equal to the normal liver). Up to 40 (3.4%) had heterogeneous SSTR expression on PET/CT: 26 (2.2%) displayed the coexistence of strongly avid lesions with the absence or near absence of SSTR uptake in measurable tumors (heterogeneous strong), while 14 (1.2%) had a combination of absent and weakly expressing SSTR tumors (heterogeneous low). An additional nine cases with prior homogeneous expression (0.8%) developed new SSTR-negative tumors along with disease progression, potentially indicating dedifferentiation. The absent or heterogeneous SSTR expression rates were greater in NET G3 than G1/G2 and in tumors originating outside the small bowel (midgut). Most NETs with absent or heterogeneous SSTR expression were fluorodeoxyglucose-F-18 ([F]FDG)-avid. The large majority of metastatic GEP-NETs demonstrate strong and relatively uniform SSTR expression, but approximately 8% are SSTR-negative, weak or heterogeneous on PET/CT. Higher than average rates of absent/heterogeneous/weak SSTR expression occur in G3 NETs and lower rates among small intestine primaries.
关于使用现代成像技术并按原发部位和肿瘤分级（G）分层的转移性胃肠胰神经内分泌肿瘤（GEP-NETs）的生长抑素受体（SSTR）表达的数据有限。在确定冷和放射性标记的生长抑素类似物治疗的相关性时，了解SSTR表达模式和肿瘤异质性至关重要。对2016年9月至2024年6月接受镓-68（[Ga]）-DOTATATE或铜-64（[Cu]）-DOTATATE正电子发射断层扫描（PET）成像的转移性高分化G1-3级GEP-NET患者进行了单机构回顾性分析。共有1192例患者被认为符合本研究条件。其中，26例（2.2%）在SSTR PET/计算机断层扫描（CT）上完全阴性，27例（2.3%）摄取较弱（低于或等于正常肝脏）。多达40例（3.4%）在PET/CT上有SSTR异质性表达：26例（2.2%）在可测量肿瘤中显示出强烈摄取病变与SSTR摄取缺失或几乎缺失并存（异质性强），而14例（1.2%）有SSTR缺失和弱表达肿瘤的组合（异质性低）。另外9例先前表达均匀的病例（0.8%）随着疾病进展出现了新的SSTR阴性肿瘤，这可能表明去分化。NET G3中SSTR缺失或异质性表达率高于G1/G2，且在起源于小肠（中肠）以外的肿瘤中更高。大多数SSTR缺失或异质性表达的NETs是氟脱氧葡萄糖-F-18（[F]FDG）摄取阳性的。大多数转移性GEP-NETs表现出强烈且相对均匀的SSTR表达，但约8%在PET/CT上为SSTR阴性、弱阳性或异质性。G3级NETs中SSTR缺失/异质性/弱表达的发生率高于平均水平，小肠原发性肿瘤中的发生率较低。
