Targeting integrin αvβ6 with gallium-68 tris (hydroxypyridinone) based PET probes

Giuseppe Floresta; Siham Memdouh; Truc Pham; Michelle T Ma; Philip J Blower; Robert C Hider; Vincenzo Abbate; Agostino Cilibrizzi

doi:10.1039/d2dt00980c

Targeting integrin αvβ6 with gallium-68 tris (hydroxypyridinone) based PET probes

Giuseppe Floresta, Siham Memdouh, Truc Pham, Michelle T Ma, Philip J Blower, Robert C Hider, Vincenzo Abbate, Agostino Cilibrizzi

Centre for Therapeutic Innovation

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Abstract

Expression of the cellular transmembrane receptor αvβ6 integrin is mostly restricted to malignant epithelial cells in a wide variety of carcinomas, including pancreatic and others derived from epithelial tissues. Thus, this protein is considered an attractive target for tumour imaging and therapy. Two different 68Ga hexadentate tris (3,4-hydroxypyridinone) (THP) chelators were produced in this study and coupled to the αvβ6 integrin-selective peptide cyclo(FRGDLAFp(NMe)K) via NHS chemistry. Radiolabelling experiments confirmed a high radiochemical yield of the two PET probes. In addition, cellular binding studies showed high binding affinities in the nanomolar range. The two integrin αvβ6-peptide-THP synthesized and radiolabeled in this study will facilitate in vivo monitoring of transmembrane receptor αvβ6 integrin by using the advantage of THP chemistry for rapid, efficient and stable gallium chelation.

Original language	English
Pages (from-to)	12796-12803
Number of pages	8
Journal	Dalton transactions (Cambridge, England : 2003)
Volume	51
Issue number	34
Early online date	11 Aug 2022
DOIs	https://doi.org/10.1039/d2dt00980c
Publication status	Published - 30 Aug 2022

ASJC Scopus subject areas

Inorganic Chemistry

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title = "Targeting integrin αvβ6 with gallium-68 tris (hydroxypyridinone) based PET probes",

abstract = "Expression of the cellular transmembrane receptor αvβ6 integrin is mostly restricted to malignant epithelial cells in a wide variety of carcinomas, including pancreatic and others derived from epithelial tissues. Thus, this protein is considered an attractive target for tumour imaging and therapy. Two different 68Ga hexadentate tris (3,4-hydroxypyridinone) (THP) chelators were produced in this study and coupled to the αvβ6 integrin-selective peptide cyclo(FRGDLAFp(NMe)K) via NHS chemistry. Radiolabelling experiments confirmed a high radiochemical yield of the two PET probes. In addition, cellular binding studies showed high binding affinities in the nanomolar range. The two integrin αvβ6-peptide-THP synthesized and radiolabeled in this study will facilitate in vivo monitoring of transmembrane receptor αvβ6 integrin by using the advantage of THP chemistry for rapid, efficient and stable gallium chelation.",

author = "Giuseppe Floresta and Siham Memdouh and Truc Pham and Ma, {Michelle T} and Blower, {Philip J} and Hider, {Robert C} and Vincenzo Abbate and Agostino Cilibrizzi",

note = "Funding Information: GF has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 893784. AC acknowledges funding from The Royal Society – International Exchanges 2021 (IEC\R2\212003) and Dr A Guerriero (CNR-ICCOM, Florence) for useful discussion on this research. This research was supported by a Cancer Research UK Career Establishment Award (C63178/A24959), King's College London & Imperial College London EPSRC Centre for Doctoral Training in Medical Imaging (EP/L015226/1), the EPSRC programme for Next Generation Molecular Imaging and Therapy with Radionuclides (EP/S032789/1, “MITHRAS”), Rosetrees Trust (M685, M606), the Wellcome Multiuser Equipment Radioanalytical Facility funded by Wellcome Trust (212885/Z/18/Z), and the Centre for Medical Engineering funded by the Wellcome Trust and the Engineering and Physical Science Research Council (WT088641/Z/09/Z). ",

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AU - Floresta, Giuseppe

AU - Memdouh, Siham

AU - Pham, Truc

AU - Ma, Michelle T

AU - Blower, Philip J

AU - Hider, Robert C

AU - Abbate, Vincenzo

AU - Cilibrizzi, Agostino

N1 - Funding Information: GF has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 893784. AC acknowledges funding from The Royal Society – International Exchanges 2021 (IEC\R2\212003) and Dr A Guerriero (CNR-ICCOM, Florence) for useful discussion on this research. This research was supported by a Cancer Research UK Career Establishment Award (C63178/A24959), King's College London & Imperial College London EPSRC Centre for Doctoral Training in Medical Imaging (EP/L015226/1), the EPSRC programme for Next Generation Molecular Imaging and Therapy with Radionuclides (EP/S032789/1, “MITHRAS”), Rosetrees Trust (M685, M606), the Wellcome Multiuser Equipment Radioanalytical Facility funded by Wellcome Trust (212885/Z/18/Z), and the Centre for Medical Engineering funded by the Wellcome Trust and the Engineering and Physical Science Research Council (WT088641/Z/09/Z).

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N2 - Expression of the cellular transmembrane receptor αvβ6 integrin is mostly restricted to malignant epithelial cells in a wide variety of carcinomas, including pancreatic and others derived from epithelial tissues. Thus, this protein is considered an attractive target for tumour imaging and therapy. Two different 68Ga hexadentate tris (3,4-hydroxypyridinone) (THP) chelators were produced in this study and coupled to the αvβ6 integrin-selective peptide cyclo(FRGDLAFp(NMe)K) via NHS chemistry. Radiolabelling experiments confirmed a high radiochemical yield of the two PET probes. In addition, cellular binding studies showed high binding affinities in the nanomolar range. The two integrin αvβ6-peptide-THP synthesized and radiolabeled in this study will facilitate in vivo monitoring of transmembrane receptor αvβ6 integrin by using the advantage of THP chemistry for rapid, efficient and stable gallium chelation.

AB - Expression of the cellular transmembrane receptor αvβ6 integrin is mostly restricted to malignant epithelial cells in a wide variety of carcinomas, including pancreatic and others derived from epithelial tissues. Thus, this protein is considered an attractive target for tumour imaging and therapy. Two different 68Ga hexadentate tris (3,4-hydroxypyridinone) (THP) chelators were produced in this study and coupled to the αvβ6 integrin-selective peptide cyclo(FRGDLAFp(NMe)K) via NHS chemistry. Radiolabelling experiments confirmed a high radiochemical yield of the two PET probes. In addition, cellular binding studies showed high binding affinities in the nanomolar range. The two integrin αvβ6-peptide-THP synthesized and radiolabeled in this study will facilitate in vivo monitoring of transmembrane receptor αvβ6 integrin by using the advantage of THP chemistry for rapid, efficient and stable gallium chelation.

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JF - Dalton transactions (Cambridge, England : 2003)

IS - 34

ER -

Targeting integrin αvβ6 with gallium-68 tris (hydroxypyridinone) based PET probes

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