Direct comparison of [ 18F]AlF-NOTA-JR11 and [ 18F]AlF-NOTA-octreotide for PET imaging of neuroendocrine tumors: Antagonist versus agonist.

Stephen Ahenkorah, Christopher Cawthorne, Erika Murce, Christophe M Deroose, Thomas Cardinaels, Yann Seimbille, Guy Bormans, Maarten Ooms, Frederik Cleeren*

*Corresponding author for this work

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BACKGROUND: [ 18F]AlF-NOTA-octreotide is an 18F-labeled somatostatin analogue which is a good clinical alternative for 68Ga-labeled somatostatin analogues. However, radiolabeled somatostatin receptor (SSTR) antagonists might outperform agonists regarding imaging sensitivity of neuroendocrine tumors (NETs). No direct comparison between the antagonist [ 18F]AlF-NOTA-JR11 and the agonist [ 18F]AlF-NOTA-octreotide as SSTR PET probes is available. Herein, we present the radiosynthesis of [ 18F]AlF-NOTA-JR11 and compare its NETs imaging properties directly with the established agonist radioligand [ 18F]AlF-NOTA-octreotide preclinically.

METHODS: [ 18F]AlF-NOTA-JR11 was synthesized in an automated synthesis module. The in vitro binding characteristics (IC 50) of [ natF]AlF-NOTA-JR11 and [ natF]AlF-NOTA-octreotide were evaluated and the in vitro stability of [ 18F]AlF-NOTA-JR11 was determined in human serum. In vitro cell binding and internalization was performed with [ 18F]AlF-NOTA-JR11 and [ 18F]AlF-NOTA-octreotide using SSTR2 expressing cells and the pharmacokinetics were evaluated using μPET/CT in mice bearing BON1.SSTR2 tumor xenografts.

RESULTS: Excellent binding affinity for SSTR2 was found for [ natF]AlF-NOTA-octreotide (IC 50 of 25.7 ± 7.9 nM). However, the IC 50 value for [ natF]AlF-NOTA-JR11 (290.6 ± 71 nM) was 11-fold higher compared to [ natF]AlF-NOTA-octreotide, indicating lower affinity for SSTR2. [ 18F]AlF-NOTA-JR11 was obtained in a good RCY (50 ± 6 %) but with moderate RCP of 94 ± 1 %. [ 18F]AlF-NOTA-JR11 demonstrated excellent stability in human serum (>95 % after 240 min). 2.7-fold higher cell binding was observed for [ 18F]AlF-NOTA-JR11 as compared to [ 18F]AlF-NOTA-octreotide after 60 min. μPET/CT images demonstrated comparable pharmacokinetics and tumor uptake between [ 18F]AlF-NOTA-JR11 (SUV max: 3.7 ± 0.8) and [ 18F]AlF-NOTA-octreotide (SUV max: 3.6 ± 0.4).

CONCLUSIONS: [ 18F]AlF-NOTA-JR11 was obtained in good RCY, albeit with a moderate RCP. The cell binding study showed significant higher binding of [ 18F]AlF-NOTA-JR11 compared to [ 18F]AlF-NOTA-octreotide, despite the higher IC 50 value of AlF-NOTA-JR11. However, pharmacokinetics and in vivo tumor uptake was comparable for both radiotracers. Novel Al 18F-labeled derivatives of JR11 with higher SSTR2 affinity should be developed for increased tumor uptake and NET imaging sensitivity.

Original languageEnglish
Article number108338
JournalNuclear Medicine and Biology
Publication statusPublished - 1 Mar 2023

Bibliographical note

Funding Information:
SCK CEN Academy support is gratefully acknowledged. This research was funded by the Education and Research Foundation for Nuclear Medicine and Molecular imaging and Neuroendocrine Tumor Research Foundation (Nuclear Medicine Pilot research grant in Neuroendocrine Tumors, F. Cleeren) and by internal funding KU Leuven . Christophe M. Deroose is a Senior Clinical Investigator at the FWO. Christopher Cawthorne was funded by FWO I000321N as well as the Department of Imaging and Pathology at KU Leuven .

Publisher Copyright:
© 2023


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