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68Ga-Trivehexin: Current Status of αvβ6-Integrin Imaging and Perspectives
by
, , , , , , ,
Luca Urso
1,2,†
,
Rebecca Napolitano
3,†, 
Giorgia Speltri
4,
Murat Tuncel
5,
Ilham Badrane
1,2,*,
Licia Uccelli
1,2
,
Francesca Porto
1,
Petra Martini
3
,
Alessandro Niorettini
3,
Corrado Cittanti
1,2,
Mirco Bartolomei
2 and
Alessandra Boschi
4
1
Department of Translational Medicine, University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy
2
Nuclear Medicine Unit, Department of Onco-Haematology, Via Aldo Moro 8, 44124 Ferrara, Italy
3
Department of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy
4
Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy
5
Department of Nuclear Medicine, Hacettepe University, 06230 Ankara, Turkey
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2025, 17(9), 1504; https://doi.org/10.3390/cancers17091504
Submission received: 8 April 2025
/
Revised: 28 April 2025
/
Accepted: 28 April 2025
/
Published: 29 April 2025
(This article belongs to the Special Issue Advances in Imaging Techniques of Molecular Oncology)
Simple Summary
Significant advancements have been made in molecular imaging, particularly positron emission tomography (PET), which has evolved from using metabolic radiotracers like 2-deoxy-2-[18F]fluoro-D-glucose [18F]FDG to more targeted probes. Among these, αvβ6-integrin has emerged as a promising target for both oncological and non-oncological diseases. This review explores the radiochemical properties and initial clinical applications of the PET probe [68Ga]Ga-Trivehexin. Preclinical and clinical studies are discussed, focusing on its radiochemical characteristics and preliminary clinical uses, highlighting advancements, challenges, and future potential. The results show that the optimized multimeric system significantly improved pharmacokinetic properties, binding affinity, and selectivity for αvβ6-integrin, achieving up to an 18-fold enhancement compared to previous monomeric tracers. Preliminary clinical applications, particularly in head and neck cancer and pancreatic adenocarcinoma, have demonstrated promising detection rates and improved differential diagnosis compared to [18F]FDG. Additionally, [68Ga]Ga-Trivehexin has shown potential in non-oncological conditions such as idiopathic pulmonary fibrosis and primary hyperthyroidism. This review emphasizes the progress made in the design and application of [68Ga]Ga-Trivehexin, a highly promising PET tracer for both oncological and non-oncological imaging.
Abstract
Background/Objectives: Molecular imaging, especially PET, has advanced significantly, shifting from metabolic radiotracers like 2-deoxy-2-[18F]fluoro-D-glucose [18F]FDG to target-specific probes. Among these, αvβ6-integrin has emerged as a promising target in cancer and non-cancer diseases. This review focuses on the radiochemical properties and initial clinical applications of the [68Ga]Ga-Trivehexin PET probe. Methods: The literature review on [68Ga]Ga-Trivehexin systematically evaluated both preclinical and clinical studies, with particular emphasis on its radiochemical characteristics and preliminary clinical applications, while highlighting advancements, associated challenges, and the potential for future developments in the field. Results: This study highlights the significant advancements achieved with [68Ga]Ga-Trivehexin in the field of molecular imaging. The optimized multimeric system has substantially enhanced the radiotracer’s pharmacokinetic properties, binding affinity, and selectivity for αvβ6 integrin, demonstrating up to an 18-fold improvement compared to previous monomeric tracers. The synthesis protocol has been refined to achieve high radiochemical purity (>95%), essential for safe clinical use. Preliminary clinical applications, particularly in head and neck cancer (HNC) and pancreatic ductal adenocarcinoma (PDAC), have shown promising results, with high detection rates and improved differential diagnosis compared to [18F]FDG. Furthermore, [68Ga]Ga-Trivehexin PET/CT has shown potential in non-oncological conditions, such as idiopathic pulmonary fibrosis (IPF) and primary hyperthyroidism, suggesting broader clinical applicability. Conclusions: [68Ga]Ga-Trivehexin is a promising PET probe for imaging αvβ6-integrin in cancers and non-oncological diseases like idiopathic pulmonary fibrosis (IPF) and primary hyperparathyroidism (PHP).
Keywords:
[68Ga]Ga-Trivehexin; trivehexin; αvβ6-integrin; molecular imaging; precision oncology; PET
