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

  • Molecules. 2022 Oct 12;27(20):6818. doi: 10.3390/molecules27206818.
Johan Hygum Dam  1  2 ,  Niels Langkjær  1 ,  Christina Baun  1 ,  Birgitte Brinkmann Olsen  3 ,  Aaraby Yoheswaran Nielsen  1 ,  Helge Thisgaard  1  2
Affiliations
  • 1. Department of Nuclear Medicine, Odense University Hospital, Kløvervænget 47, DK-5000 Odense, Denmark.
  • 2. Department of Clinical Research, University of Southern Denmark, J.B. Winsløws Vej 19, DK-5000 Odense, Denmark.
  • 3. Department of Surgical Pathology, Zealand University Hospital, Sygehusvej 10, DK-4000 Roskilde, Denmark.
PMID: 36296411 DOI: 10.3390/molecules27206818
Abstract

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-Nal3]-Octreotide and compares it in vivo to DOTA- and NOTA-[1-Nal3]-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.

Keywords
AlF; F-18; PET; gallium-68; neuroendocrine; octreotide.
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