Ilhan Harun, Lindner S, Todica A, Cyran C C, Tiling R, Auernhammer C J, Spitzweg C, Boeck S, Unterrainer M, Gildehaus F J, Böning G, Jurkschat K, Wängler C, Wängler B, Schirrmacher R, Bartenstein P
Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany.
ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System at the University Hospital of Munich (GEPNET-KUM), University Hospital of Munich, Munich, Germany.
Eur J Nucl Med Mol Imaging. 2020 Apr;47(4):870-880. doi: 10.1007/s00259-019-04501-6. Epub 2019 Sep 6.
PET/CT using Ga-labeled somatostatin analogs (SSA) targeting somatostatin receptors (SSR) on the cell surface of well-differentiated neuroendocrine tumors (NET) represents the clinical reference standard for imaging. However, economic and logistic challenges of the Ge/Ga generator-based approach have disadvantages over F-labeled compounds. Here, we present the first in-human data of F-SiFAlin-TATE, a novel F-labeled, SSR-targeting peptide. The aim was to compare the intra-individual biodistribution, tumor uptake, and image quality of F-SiFAlin-TATE to the clinical reference standard Ga-DOTA-TOC.
Thirteen patients with NET staged with both Ga-DOTA-TOC and F-SiFAlin-TATE PET/CT have been included in this retrospective analysis. We compared the biodistribution in normal organs and tumor uptake of NET lesions by SUVmean and SUVmax measurement for tracers. Additionally mean and max tumor-to-liver (TLR) and tumor-to-spleen ratios (TSR) have been calculated by division of SUVmean and SUVmax of tumor lesions by the SUVmean of the liver and spleen, respectively. Additionally, image quality was visually rated by 5 blinded readers and an intra-class correlation (ICC) analysis on inter-observer agreement has been performed.
Compared with Ga-DOTA-TOC, the biodistribution of F-SiFAlin-TATE showed somewhat higher, however, statistically not significant higher uptake in the liver, spleen, and adrenal glands. Significantly higher uptake was observed in the kidneys. Tumor uptake was higher in most tumor lesions with significantly higher uptake in common metastatic sites of NET including the liver (SUVmax 18.8 ± 8.4 vs. 12.8 ± 5.6; p < 0.001), lymph nodes (SUVmax 23.8 ± 20.7 vs. 17.4 ± 16.1; p < 0.001) and bone (SUVmax 16.0 ± 10.1 vs. 10.3 ± 5.7; p < 0.01) for F-SiFAlin-TATE. The high tumor uptake resulted in favorable TLR and TSR, comparable with that of Ga-DOTA-TOC. The ICC analysis on the inter-observer agreement on image quality was substantial and almost perfect. Image quality was rated as excellent in most cases in both Ga-DOTA-TOC and F-SiFAlin-TATE PET.
The favorable characteristics of F-SiFAlin-TATE with a high image quality, the kit-like labeling procedure, and the promising clinical performance enable improved logistics and diagnostic possibilities for PET imaging of NET. Our first clinical results warrant further systematic studies investigating the clinical use of F-SiFAlin-TATE in NET patients.
使用镓标记的生长抑素类似物（SSA）靶向分化良好的神经内分泌肿瘤（NET）细胞表面的生长抑素受体（SSR）的PET/CT是成像的临床参考标准。然而，基于锗/镓发生器方法的经济和后勤挑战使其相对于氟标记化合物存在劣势。在此，我们展示了新型氟标记的、靶向SSR的肽F-SiFAlin-TATE的首例人体数据。目的是比较F-SiFAlin-TATE与临床参考标准镓-多胺基多羧基-奥曲肽（Ga-DOTA-TOC）的个体内生物分布、肿瘤摄取及图像质量。
本回顾性分析纳入了13例接受过Ga-DOTA-TOC和F-SiFAlin-TATE PET/CT检查的NET患者。我们通过测量示踪剂的SUVmean和SUVmax来比较正常器官中的生物分布以及NET病变的肿瘤摄取情况。此外，通过将肿瘤病变的SUVmean和SUVmax分别除以肝脏和脾脏的SUVmean，计算出平均和最大肿瘤与肝脏（TLR）及肿瘤与脾脏的比率（TSR）。另外，由5名不知情的阅片者对图像质量进行视觉评分，并对观察者间的一致性进行组内相关系数（ICC）分析。
与Ga-DOTA-TOC相比，F-SiFAlin-TATE的生物分布在肝脏、脾脏和肾上腺中的摄取略高，但在统计学上无显著差异。在肾脏中观察到摄取显著更高。大多数肿瘤病变中的肿瘤摄取更高，在NET常见转移部位包括肝脏（SUVmax 18.8±8.4 vs. 12.8±5.6；p<0.001）、淋巴结（SUVmax 23.8±20.7 vs. 17.4±16.1；p<0.001）和骨骼（SUVmax 16.0±10.1 vs. 10.3±5.7；p<0.01）中，F-SiFAlin-TATE的摄取显著更高。高肿瘤摄取导致了良好的TLR和TSR，与Ga-DOTA-TOC相当。对图像质量观察者间一致性的ICC分析显示一致性程度较高且几乎完美。在Ga-DOTA-TOC和F-SiFAlin-TATE PET的大多数情况下，图像质量被评为优秀。
F-SiFAlin-TATE具有良好的特性，包括高图像质量、试剂盒样标记程序以及有前景的临床性能，这使得NET的PET成像在后勤保障和诊断可能性方面得到改善。我们的首例临床结果值得进一步开展系统研究，以探究F-SiFAlin-TATE在NET患者中的临床应用。
