CC BY 4.0 · World J Nucl Med 2023; 22(02): 152-170
DOI: 10.1055/s-0043-1769961
Presentation Abstracts

3p-C-NETA-TATE: A Potential Somatostatin Analogue for Diagnostic and Therapeutic SSTR2 Targeting Radiopharmaceuticals

Stephen Ahenkorah
1   KU Leuven, Belgium
,
Erica Murce
2   Erasmus MC, the Netherlands
,
Cawthorne Christopher
1   KU Leuven, Belgium
,
Yann Seimbille
2   Erasmus MC, the Netherlands
,
Thomas Cardinaels
3   SCK CEN, Belgium
,
Christophe M. Deroose
1   KU Leuven, Belgium
,
Guy Bormans
1   KU Leuven, Belgium
,
Maarten Ooms
3   SCK CEN, Belgium
,
Frederik Cleeren
1   KU Leuven, Belgium
› Author Affiliations
› Further Information
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stephen.ahenkorah@kuleuven.be

Introduction: Somatostatin-based radiopharmaceuticals (e.g., [68Ga] Ga-DOTATATE and [177Lu] Lu-DOTATATE) have been used successfully to diagnose, monitor, and treat patients with neuroendocrine tumors. [18F] AlF-NOTA-octreotide, a promising 18F-labeled somatostatin analogue and potential replacement for 68Ga-DOTA-peptides, is currently being studied in clinical trials.1 However, ideally, the same precursor (combination of chelator-linker-vector) can be used to produce both diagnostic and therapeutic radioprobes with pharmacokinetic properties that are very similar (e.g., Al18F/213Bi/177Lu) or identical (e.g., complementary Tb-radionuclides), allowing for accurate personalized dosimetry estimation and radionuclide therapy of NET patients.2 We evaluated the potentially versatile and effective chelator 3p-C-NETA in this study and present preliminary results of radiosynthesis and preclinical evaluation of [18F]AlF-3p-C-NETA-TATE.3

Methods: At varying temperatures, 3p-C-NETA was radiolabeled with diagnostic (68Ga, Al18F) or therapeutic (177Lu, 161Tb, and 213Bi) radionuclides. The in vitro stability of the corresponding radiocomplexes in human serum at 37°C was determined. 3p-C-NETA-TATE was produced via standard solid/liquid-phase peptide synthesis and purified via HPLC. [18F]AlF-3p-C-NETA-TATE was synthesized in an automated AllinOne synthesis module (Trasis, Belgium), radio-HPLC was used to analyze it, and the in vitro stability of [18F]AlF-3p-C-NETA-TATE was investigated. At 37°C, [18F] AlF-3p-C-NETA-TATE was tested in formulation buffer, PBS, and human serum. [18F] AlF-3p-C-NETA-TATE was used to perform in vitro cell binding and internalization. The pharmacokinetics of [18F] AlF-3p-C-NETA-TATE were evaluated using PET/MRI and PET/CT in healthy rats and mice bearing BON1.SSTR2 xenografts, respectively, with [18F] AlF-NOTA-octreotide as a benchmark.1

Results: At 25°C, 3p-C-NETA was efficiently labeled with 177Lu and 213Bi (RCY > 95%), and at 55°C, with 161Tb (> 95%) and 68Ga (> 90%). To achieve good yields (> 85%), Al18F-labeling required 95°C. Over an 8-day period, the 177Lu- and 161Tb-3p-C-NETA-complexes demonstrated excellent in vitro stability in human serum (97% intact). We also found that [18F] AlF-3p-C-NETA has a high in vitro stability (> 93% intact in human serum) for up to 2 hours. [68Ga] Ga-3p-C-NETA demonstrated low stability in human serum (80% intact after 2 hours). [18F] AlF-3p-C-NETA-TATE was synthesized with high RCY (56%) and radiochemical purity (> 98%). In all tested conditions, [18F] AlF-3p-C-NETA-TATE demonstrated excellent in vitro stability with greater than 95% intact tracer after 4 hours. After 60 minutes of incubation with [18F] AlF-3p-C-NETA-TATE, high SSTR2-specific cell binding and internalization (16.3 ± 1.9% of which 80.1 ± 1.9% is internalized) was observed. Finally, [18F] AlF-3p-C-NETA-TATE demonstrated excellent pharmacokinetic properties and tumor accumulation comparable to [18F] AlF-NOTA-Octreotide.

Conclusions: 3p-C-NETA is a versatile chelator that can be used for both targeted radionuclide therapy (177Lu, 213Bi, 161Tb) and diagnostic applications (Al18F), and it has the potential to replace DOTA analogues currently in clinical use. [18F] AlF-3p-C-NETA-TATE and [213Bi]-Bi-3p-C-NETA-TATE will be studied further as a potential theranostic pair in SSTR2 tumor-bearing mice.



Publication History

Article published online:
25 May 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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  • References

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  • 2 Ahenkorah S, Cassells I, Deroose CM, et al. Bismuth-213 for targeted radionuclide therapy: from atom to bedside. Pharmaceutics 2021;13(5):599
  • 3 Ahenkorah S, Murce E, Cawthorne C, et al. 3p-C-NETA: a versatile and effective chelator for development of Al18F-labeled and therapeutic radiopharmaceuticals. Theranostics 2022;12(13):5971–5985