Department of Nuclear Medicine, Odense University Hospital, Kløvervænget 47, DK-5000 Odense, Denmark.
Department of Clinical Research, University of Southern Denmark, J.B. Winsløws Vej 19, DK-5000 Odense, Denmark.
Molecules. 2022 Oct 12;27(20):6818. doi: 10.3390/molecules27206818.
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]AlF-NOTA-[1-Nal]-Octreotide and compares it in vivo to DOTA- and NOTA-[1-Nal]-Octreotide radiolabeled with gallium-68.
DOTA- and NOTA-NOC were radiolabeled with gallium-68 and NOTA-NOC with [F]AlF. Biodistributions of the three radioligands were evaluated in AR42J xenografted mice at 1 h p.i and for [F]AlF at 3 h p.i. Preclinical PET/CT was applied to confirm the general uptake pattern.
Gallium-68 was incorporated into DOTA- and NOTA-NOC in yields and radiochemical purities greater than 96.5%. NOTA-NOC was radiolabeled with [F]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]Ga-DOTA-NOC and 25.7 ± 5.8 %ID/g for [Ga]Ga-NOTA-NOC. Additionally, [F]AlF-NOTA-NOC exhibited a tumor uptake of 37.3 ± 10.5 %ID/g for [F]AlF-NOTA-NOC, which further increased to 42.1 ± 5.3 %ID/g at 3 h p.i.
The high tumor uptake of all radioligands was observed. However, [F]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]AlF-NOTA-NOC, making it possible to detect liver metastases. Therefore, [F]AlF demonstrates promise as a surrogate pseudo-radiometal to gallium-68.
生长抑素受体 1-5 在神经内分泌肿瘤中过度表达，因此成为分子成像的有利靶点。本研究探讨了 [F]AlF-NOTA-[1-Nal]-奥曲肽的潜力，并将其与镓-68 标记的 DOTA-和 NOTA-[1-Nal]-奥曲肽进行了体内比较。
用镓-68 标记 DOTA-和 NOTA-NOC，用 [F]AlF 标记 NOTA-NOC。在 AR42J 异种移植瘤小鼠中，于 1 h p.i. 评估三种放射性配体的生物分布，并于 3 h p.i. 评估 [F]AlF 的生物分布。应用临床前 PET/CT 确认一般摄取模式。
镓-68 以大于 96.5%的产率和放射化学纯度掺入 DOTA-和 NOTA-NOC。NOTA-NOC 用 [F]AlF 标记，产率为 38±8%，放射化学纯度大于 99%，经纯化后。荷瘤小鼠的生物分布显示，[Ga]Ga-DOTA-NOC 的肿瘤摄取率为 26.4±10.8%ID/g，[Ga]Ga-NOTA-NOC 的肿瘤摄取率为 25.7±5.8%ID/g。此外，[F]AlF-NOTA-NOC 的肿瘤摄取率为 37.3±10.5%ID/g，3 h p.i. 时进一步增加至 42.1±5.3%ID/g。
观察到所有放射性配体的高肿瘤摄取。然而，[F]AlF-NOTA-NOC 在体内超过了其他临床上广泛应用的放射性示踪剂，特别是在 3 h p.i. 时。[F]AlF-NOTA-NOC 的肿瘤与血液和肝脏的比值在 3 小时内显著增加，这使得检测肝转移成为可能。因此，[F]AlF 有望成为镓-68 的替代拟放射性金属。
