Biodistribution and first clinical results of 18 F-SiFAlin-TATE PET: a novel 18 F-labeled somatostatin analog for imaging of neuroendocrine tumors.

Introduction: PET/CT using ⁶⁸ 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 ⁶⁸ Ge/ ⁶⁸ Ga generator-based approach have disadvantages over ¹⁸ F-labeled compounds. Here, we present the first in-human data of ¹⁸ F-SiFAlin-TATE, a novel ¹⁸ F-labeled, SSR-targeting peptide. The aim was to compare the intra-individual biodistribution, tumor uptake, and image quality of ¹⁸ F-SiFAlin-TATE to the clinical reference standard ⁶⁸ Ga-DOTA-TOC.
Methods: Thirteen patients with NET staged with both ⁶⁸ Ga-DOTA-TOC and ¹⁸ 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.
Results: Compared with ⁶⁸ Ga-DOTA-TOC, the biodistribution of ¹⁸ 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 ¹⁸ F-SiFAlin-TATE. The high tumor uptake resulted in favorable TLR and TSR, comparable with that of ⁶⁸ 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 ⁶⁸ Ga-DOTA-TOC and ¹⁸ F-SiFAlin-TATE PET.
Conclusion: The favorable characteristics of ¹⁸ 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 ¹⁸ F-SiFAlin-TATE in NET patients.