Preparation and Evaluation of [¹⁸F]AlF-NOTA-NOC for PET Imaging of Neuroendocrine Tumors: Comparison to [⁶⁸Ga]Ga-DOTA/NOTA-NOC

Background: The somatostatin receptors 1-5 are overexpressed on neuroendocrine neoplasms and, as such, represent a favorable target for molecular imaging. This study investigates the potential of [F-18]AlF-NOTA-[1-Nal(3)]-Octreotide and compares it in vivo to DOTA- and NOTA-[1-Nal(3)]-Octreotide radiolabeled with gallium-68. Methods: DOTA- and NOTA-NOC were radiolabeled with gallium-68 and NOTA-NOC with [F-18]AlF. Biodistributions of the three radioligands were evaluated in AR42J xenografted mice at 1 h p.i and for [F-18]AlF at 3 h p.i. Preclinical PET/CT was applied to confirm the general uptake pattern. Results: Gallium-68 was incorporated into DOTA- and NOTA-NOC in yields and radiochemical purities greater than 96.5%. NOTA-NOC was radiolabeled with [F-18]AlF in yields of 38 +/- 8% and radiochemical purity above 99% after purification. The biodistribution in tumor-bearing mice showed a high uptake in tumors of 26.4 +/- 10.8 %ID/g for [Ga-68]Ga-DOTA-NOC and 25.7 +/- 5.8 %ID/g for [Ga-68]Ga-NOTA-NOC. Additionally, [F-18]AlF-NOTA-NOC exhibited a tumor uptake of 37.3 +/- 10.5 %ID/g for [F-18]AlF-NOTA-NOC, which further increased to 42.1 +/- 5.3 %ID/g at 3 h p.i. Conclusions: The high tumor uptake of all radioligands was observed. However, [F-18]AlF-NOTA-NOC surpassed the other clinically well-established radiotracers in vivo, especially at 3 h p.i. The tumor-to-blood and -liver ratios increased significantly over three hours for [F-18]AlF-NOTA-NOC, making it possible to detect liver metastases. Therefore, [F-18]AlF demonstrates promise as a surrogate pseudo-radiometal to gallium-68.