Background: [F]AlF-NOTA-octreotide is an F-labeled somatostatin analogue which is a good clinical alternative for Ga-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 [F]AlF-NOTA-JR11 and the agonist [F]AlF-NOTA-octreotide as SSTR PET probes is available. Herein, we present the radiosynthesis of [F]AlF-NOTA-JR11 and compare its NETs imaging properties directly with the established agonist radioligand [F]AlF-NOTA-octreotide preclinically.
Methods: [F]AlF-NOTA-JR11 was synthesized in an automated synthesis module. The in vitro binding characteristics (IC) of [F]AlF-NOTA-JR11 and [F]AlF-NOTA-octreotide were evaluated and the in vitro stability of [F]AlF-NOTA-JR11 was determined in human serum. In vitro cell binding and internalization was performed with [F]AlF-NOTA-JR11 and [F]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 [F]AlF-NOTA-octreotide (IC of 25.7 ± 7.9 nM). However, the IC value for [F]AlF-NOTA-JR11 (290.6 ± 71 nM) was 11-fold higher compared to [F]AlF-NOTA-octreotide, indicating lower affinity for SSTR2. [F]AlF-NOTA-JR11 was obtained in a good RCY (50 ± 6 %) but with moderate RCP of 94 ± 1 %. [F]AlF-NOTA-JR11 demonstrated excellent stability in human serum (>95 % after 240 min). 2.7-fold higher cell binding was observed for [F]AlF-NOTA-JR11 as compared to [F]AlF-NOTA-octreotide after 60 min. μPET/CT images demonstrated comparable pharmacokinetics and tumor uptake between [F]AlF-NOTA-JR11 (SUV: 3.7 ± 0.8) and [F]AlF-NOTA-octreotide (SUV: 3.6 ± 0.4).
Conclusions: [F]AlF-NOTA-JR11 was obtained in good RCY, albeit with a moderate RCP. The cell binding study showed significant higher binding of [F]AlF-NOTA-JR11 compared to [F]AlF-NOTA-octreotide, despite the higher IC value of AlF-NOTA-JR11. However, pharmacokinetics and in vivo tumor uptake was comparable for both radiotracers. Novel AlF-labeled derivatives of JR11 with higher SSTR2 affinity should be developed for increased tumor uptake and NET imaging sensitivity.
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View Article and Find Full Text PDFDirect comparison of [F]AlF-NOTA-JR11 and [F]AlF-NOTA-octreotide for PET imaging of neuroendocrine tumors: Antagonist versus agonist.
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