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 [ 18F]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 [ 18F]AlF. Biodistributions of the three radioligands were evaluated in AR42J xenografted mice at 1 h p.i and for [ 18F]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 [ 18F]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 [ 68Ga]Ga-DOTA-NOC and 25.7 ± 5.8 %ID/g for [ 68Ga]Ga-NOTA-NOC. Additionally, [ 18F]AlF-NOTA-NOC exhibited a tumor uptake of 37.3 ± 10.5 %ID/g for [ 18F]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, [ 18F]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 [ 18F]AlF-NOTA-NOC, making it possible to detect liver metastases. Therefore, [ 18F]AlF demonstrates promise as a surrogate pseudo-radiometal to gallium-68.