Purpose Peptide-based probes targeting integrin αvβ6 have shown promise in clinical trials for cancer imaging based on the high over-expression of this epithelial-specific cell surface receptor in many cancerous tissues. Recently, the αvβ6-targeting gallium-68 labeled DOTA-5G peptide, [68Ga]Ga DOTA-5G, demonstrated diagnostic value in patients with metastatic pancreatic cancer. To facilitate adoption at sites without access to gallium-68 and take advantage of the characteristics of fluorine-18 through convenient [18F]fluoride chelation chemistry, this study evaluated the fluorine-18 labeled analog, [18F]AlF NOTA-5G, in vitro and in vivo in a tumor mouse model, and compared it to [68Ga]Ga DOTA-5G. Procedures NOTA-5G was synthesized on solid phase and radiolabeled with aluminum [18F]fluoride to generate [18F]AlF NOTA-5G. Cell binding and internalization of [18F]AlF NOTA-5G were evaluated in paired DX3puroβ6 (αvβ6 +) and DX3puro (αvβ6 -), and pancreatic BxPC-3 (αvβ6 +) cells. Imaging (1–6 h) and biodistribution were performed in BxPC-3 tumor-bearing mice. Results [18F]AlF NOTA-5G was obtained in > 93% radiochemical purity. Cell binding was αvβ6-targeted (1 h: 66% bound to DX3puroβ6, vs 2% to DX3puro), and ≥ 50% of bound activity was internalized; analogous to [68Ga]Ga DOTA-5G, PET imaging showed clearly delineated tumors. Excretion remained primarily renal (1 to 4 h: 18.6 to 12.5% ID/g). Tumor uptake remained relatively steady (1 to 4 h: 2.3 ± 0.4 to 1.8 ± 0.6% ID/g – closely matching [68Ga]Ga DOTA-5G with 2.6 ± 0.8 and 2.0 ± 0.6% ID/g at 1 and 2 h), resulting in tumor/pancreas, tumor/liver, and tumor/blood ratios of 18/1, 24/1, and 162/1, respectively (4 h); by comparison, for [68Ga]Ga DOTA-5G the values were 21/1, 20/1, and 22/1 (2 h). Conclusions [18F]AlF NOTA-5G demonstrated selective αvβ6-targeting and tumor uptake similar to [68Ga]Ga DOTA-5G. The tumor-to-background ratio resulted high-contrast PET images, with an extended imaging window compared to [68Ga]Ga DOTA-5G. The synthesis of [18F]AlF NOTA-5G is currently being optimized for clinical production.

Evaluation of [¹⁸F]AlF NOTA-5G, an Aluminum [¹⁸F]fluoride Labeled Peptide Targeting the Cell Surface Receptor Integrin Alpha(v)beta(6) for PET Imaging

期刊论文
发表日期：

2025年2月20日

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Sven H. Hausner,
Ryan A. Davis,
Tanushree Ganguly,
Rebecca Harris,
Julie L. Sutcliffe

摘要

Purpose

Peptide-based probes targeting integrin α_vβ₆ have shown promise in clinical trials for cancer imaging based on the high over-expression of this epithelial-specific cell surface receptor in many cancerous tissues. Recently, the α_vβ₆-targeting gallium-68 labeled DOTA-5G peptide, [⁶⁸Ga]Ga DOTA-5G, demonstrated diagnostic value in patients with metastatic pancreatic cancer. To facilitate adoption at sites without access to gallium-68 and take advantage of the characteristics of fluorine-18 through convenient [¹⁸F]fluoride chelation chemistry, this study evaluated the fluorine-18 labeled analog, [¹⁸F]AlF NOTA-5G, in vitro and in vivo in a tumor mouse model, and compared it to [⁶⁸Ga]Ga DOTA-5G.

Procedures

NOTA-5G was synthesized on solid phase and radiolabeled with aluminum [¹⁸F]fluoride to generate [¹⁸F]AlF NOTA-5G. Cell binding and internalization of [¹⁸F]AlF NOTA-5G were evaluated in paired DX3puroβ6 (α_vβ₆ +) and DX3puro (α_vβ₆ -), and pancreatic BxPC-3 (α_vβ₆ +) cells. Imaging (1–6 h) and biodistribution were performed in BxPC-3 tumor-bearing mice.

Results

[¹⁸F]AlF NOTA-5G was obtained in > 93% radiochemical purity. Cell binding was α_vβ₆-targeted (1 h: 66% bound to DX3puroβ6, vs 2% to DX3puro), and ≥ 50% of bound activity was internalized; analogous to [⁶⁸Ga]Ga DOTA-5G, PET imaging showed clearly delineated tumors. Excretion remained primarily renal (1 to 4 h: 18.6 to 12.5% ID/g). Tumor uptake remained relatively steady (1 to 4 h: 2.3 ± 0.4 to 1.8 ± 0.6% ID/g – closely matching [⁶⁸Ga]Ga DOTA-5G with 2.6 ± 0.8 and 2.0 ± 0.6% ID/g at 1 and 2 h), resulting in tumor/pancreas, tumor/liver, and tumor/blood ratios of 18/1, 24/1, and 162/1, respectively (4 h); by comparison, for [⁶⁸Ga]Ga DOTA-5G the values were 21/1, 20/1, and 22/1 (2 h).

Conclusions

[¹⁸F]AlF NOTA-5G demonstrated selective α_vβ₆-targeting and tumor uptake similar to [⁶⁸Ga]Ga DOTA-5G. The tumor-to-background ratio resulted high-contrast PET images, with an extended imaging window compared to [⁶⁸Ga]Ga DOTA-5G. The synthesis of [¹⁸F]AlF NOTA-5G is currently being optimized for clinical production.

Evaluation of [18F]AlF NOTA-5G, an Aluminum [18F]fluoride Labeled Peptide Targeting the Cell Surface Receptor Integrin Alpha(v)beta(6) for PET Imaging

摘要

Evaluation of [¹⁸F]AlF NOTA-5G, an Aluminum [¹⁸F]fluoride Labeled Peptide Targeting the Cell Surface Receptor Integrin Alpha(v)beta(6) for PET Imaging