In vitro and in vivo evaluation of the effects of aluminum [18F]fluoride radiolabeling on an integrin αvβ6-specific peptide

Sven H. Hausner, Nadine Bauer, Julie Sutcliffe

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Introduction: Incorporation of fluorine-18 (18F) into radiotracers by capturing ionic [18F]-species can greatly accelerate and simplify radiolabeling for this important positron emission tomography (PET) radioisotope. Among the different strategies, the incorporation of aluminum [18F]fluoride (Al[18F]2+) into NOTA chelators has recently emerged as a robust approach to peptide radiolabeling. This study presents Al[18F]2+-radiolabeling of an αvβ6 integrin-targeted peptide (NOTA-PEG28-A20FMDV2) and its in vitro and in vivo evaluation. Methods: Aluminum [18F]fluoride was prepared at r.t. from [18F]fluoride (40 MBq-11 GBq) and introduced into NOTA-PEG28-A20FMDV2 (1) in sodium acetate (pH 4.1; 100°C, 15 min). The radiotracer Al[18F] NOTA-PEG28-A20FMDV2 (2) was purified by HPLC, formulated in PBS and evaluated in vitro (stability; binding and internalization in αvβ6(+) and αvβ6(-) cells) and in vivo (paired αvβ6(+) and αvβ6(-) xenograft mice: PET/CT, biodistribution, tumor autoradiography and metabolites). Results: The radiotracer 2 was prepared in 90±6 min (incl. formulation; n=3) in 19.3±5.4% decay corrected radiochemical yield (radiochemical purity: >99%; specific activity: 158±36 GBq/μmol) and was stable in PBS and serum (2 h). During in vitro cell binding studies, 2 showed high, αvβ6-targeted binding (αvβ6(+): 42.4±1.2% of total radioactivity, ratio (+)/(-)=8.4/1) and internalization (αvβ6(+): 28.3±0.5% of total radioactivity, (+)/(-)=11.7/1). In vivo, 2 maintained αvβ6-targeted binding (biodistribution; 1 h: αvβ6(+): 1.74±0.38% ID/g, (+)/(-)=2.72/1; 4 h: αvβ6(+): 1.21±0.56% ID/g, (+)/(-)=4.0/1; 11% intact 2 in tumor at 1 h), with highest uptake around the tumor edge (autoradiography). Most of the radioactivity cleared rapidly in the urine within one hour, but a significant fraction remained trapped in the kidneys (4 h: 229±44% ID/g). Conclusion: The Al[18F]/NOTA-based radiolabeling was rapid and efficient, and the radiotracer 2 showed good αvβ6-selectivity in vitro and in vivo. However, in contrast to A20FMDV2 labeled with covalently bound [18F]-prosthetic groups (e.g., [18F]fluorobenzoic acid), 2 demonstrated significant trapping in kidneys, similar to radiometal-labeled chelator-analogs of 2.

Original languageEnglish (US)
Pages (from-to)43-50
Number of pages8
JournalNuclear Medicine and Biology
Volume41
Issue number1
DOIs
StatePublished - Jan 2014

Fingerprint

Integrins
Peptides
Radioactivity
Chelating Agents
Autoradiography
Positron-Emission Tomography
Kidney
Sodium Acetate
Neoplasms
Fluorine
Fluorides
Heterografts
Radioisotopes
High Pressure Liquid Chromatography
In Vitro Techniques
aluminum fluoride
1,4,7-triazacyclononane-N,N',N''-triacetic acid
Urine
Serum

Keywords

  • Aluminum [18F]fluoride
  • Fluorine 18
  • Integrin
  • NOTA
  • Peptide
  • Positron emission tomography

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

In vitro and in vivo evaluation of the effects of aluminum [18F]fluoride radiolabeling on an integrin αvβ6-specific peptide. / Hausner, Sven H.; Bauer, Nadine; Sutcliffe, Julie.

In: Nuclear Medicine and Biology, Vol. 41, No. 1, 01.2014, p. 43-50.

Research output: Contribution to journalArticle

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title = "In vitro and in vivo evaluation of the effects of aluminum [18F]fluoride radiolabeling on an integrin αvβ6-specific peptide",
abstract = "Introduction: Incorporation of fluorine-18 (18F) into radiotracers by capturing ionic [18F]-species can greatly accelerate and simplify radiolabeling for this important positron emission tomography (PET) radioisotope. Among the different strategies, the incorporation of aluminum [18F]fluoride (Al[18F]2+) into NOTA chelators has recently emerged as a robust approach to peptide radiolabeling. This study presents Al[18F]2+-radiolabeling of an αvβ6 integrin-targeted peptide (NOTA-PEG28-A20FMDV2) and its in vitro and in vivo evaluation. Methods: Aluminum [18F]fluoride was prepared at r.t. from [18F]fluoride (40 MBq-11 GBq) and introduced into NOTA-PEG28-A20FMDV2 (1) in sodium acetate (pH 4.1; 100°C, 15 min). The radiotracer Al[18F] NOTA-PEG28-A20FMDV2 (2) was purified by HPLC, formulated in PBS and evaluated in vitro (stability; binding and internalization in αvβ6(+) and αvβ6(-) cells) and in vivo (paired αvβ6(+) and αvβ6(-) xenograft mice: PET/CT, biodistribution, tumor autoradiography and metabolites). Results: The radiotracer 2 was prepared in 90±6 min (incl. formulation; n=3) in 19.3±5.4{\%} decay corrected radiochemical yield (radiochemical purity: >99{\%}; specific activity: 158±36 GBq/μmol) and was stable in PBS and serum (2 h). During in vitro cell binding studies, 2 showed high, αvβ6-targeted binding (αvβ6(+): 42.4±1.2{\%} of total radioactivity, ratio (+)/(-)=8.4/1) and internalization (αvβ6(+): 28.3±0.5{\%} of total radioactivity, (+)/(-)=11.7/1). In vivo, 2 maintained αvβ6-targeted binding (biodistribution; 1 h: αvβ6(+): 1.74±0.38{\%} ID/g, (+)/(-)=2.72/1; 4 h: αvβ6(+): 1.21±0.56{\%} ID/g, (+)/(-)=4.0/1; 11{\%} intact 2 in tumor at 1 h), with highest uptake around the tumor edge (autoradiography). Most of the radioactivity cleared rapidly in the urine within one hour, but a significant fraction remained trapped in the kidneys (4 h: 229±44{\%} ID/g). Conclusion: The Al[18F]/NOTA-based radiolabeling was rapid and efficient, and the radiotracer 2 showed good αvβ6-selectivity in vitro and in vivo. However, in contrast to A20FMDV2 labeled with covalently bound [18F]-prosthetic groups (e.g., [18F]fluorobenzoic acid), 2 demonstrated significant trapping in kidneys, similar to radiometal-labeled chelator-analogs of 2.",
keywords = "Aluminum [18F]fluoride, Fluorine 18, Integrin, NOTA, Peptide, Positron emission tomography",
author = "Hausner, {Sven H.} and Nadine Bauer and Julie Sutcliffe",
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volume = "41",
pages = "43--50",
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issn = "0969-8051",
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T1 - In vitro and in vivo evaluation of the effects of aluminum [18F]fluoride radiolabeling on an integrin αvβ6-specific peptide

AU - Hausner, Sven H.

AU - Bauer, Nadine

AU - Sutcliffe, Julie

PY - 2014/1

Y1 - 2014/1

N2 - Introduction: Incorporation of fluorine-18 (18F) into radiotracers by capturing ionic [18F]-species can greatly accelerate and simplify radiolabeling for this important positron emission tomography (PET) radioisotope. Among the different strategies, the incorporation of aluminum [18F]fluoride (Al[18F]2+) into NOTA chelators has recently emerged as a robust approach to peptide radiolabeling. This study presents Al[18F]2+-radiolabeling of an αvβ6 integrin-targeted peptide (NOTA-PEG28-A20FMDV2) and its in vitro and in vivo evaluation. Methods: Aluminum [18F]fluoride was prepared at r.t. from [18F]fluoride (40 MBq-11 GBq) and introduced into NOTA-PEG28-A20FMDV2 (1) in sodium acetate (pH 4.1; 100°C, 15 min). The radiotracer Al[18F] NOTA-PEG28-A20FMDV2 (2) was purified by HPLC, formulated in PBS and evaluated in vitro (stability; binding and internalization in αvβ6(+) and αvβ6(-) cells) and in vivo (paired αvβ6(+) and αvβ6(-) xenograft mice: PET/CT, biodistribution, tumor autoradiography and metabolites). Results: The radiotracer 2 was prepared in 90±6 min (incl. formulation; n=3) in 19.3±5.4% decay corrected radiochemical yield (radiochemical purity: >99%; specific activity: 158±36 GBq/μmol) and was stable in PBS and serum (2 h). During in vitro cell binding studies, 2 showed high, αvβ6-targeted binding (αvβ6(+): 42.4±1.2% of total radioactivity, ratio (+)/(-)=8.4/1) and internalization (αvβ6(+): 28.3±0.5% of total radioactivity, (+)/(-)=11.7/1). In vivo, 2 maintained αvβ6-targeted binding (biodistribution; 1 h: αvβ6(+): 1.74±0.38% ID/g, (+)/(-)=2.72/1; 4 h: αvβ6(+): 1.21±0.56% ID/g, (+)/(-)=4.0/1; 11% intact 2 in tumor at 1 h), with highest uptake around the tumor edge (autoradiography). Most of the radioactivity cleared rapidly in the urine within one hour, but a significant fraction remained trapped in the kidneys (4 h: 229±44% ID/g). Conclusion: The Al[18F]/NOTA-based radiolabeling was rapid and efficient, and the radiotracer 2 showed good αvβ6-selectivity in vitro and in vivo. However, in contrast to A20FMDV2 labeled with covalently bound [18F]-prosthetic groups (e.g., [18F]fluorobenzoic acid), 2 demonstrated significant trapping in kidneys, similar to radiometal-labeled chelator-analogs of 2.

AB - Introduction: Incorporation of fluorine-18 (18F) into radiotracers by capturing ionic [18F]-species can greatly accelerate and simplify radiolabeling for this important positron emission tomography (PET) radioisotope. Among the different strategies, the incorporation of aluminum [18F]fluoride (Al[18F]2+) into NOTA chelators has recently emerged as a robust approach to peptide radiolabeling. This study presents Al[18F]2+-radiolabeling of an αvβ6 integrin-targeted peptide (NOTA-PEG28-A20FMDV2) and its in vitro and in vivo evaluation. Methods: Aluminum [18F]fluoride was prepared at r.t. from [18F]fluoride (40 MBq-11 GBq) and introduced into NOTA-PEG28-A20FMDV2 (1) in sodium acetate (pH 4.1; 100°C, 15 min). The radiotracer Al[18F] NOTA-PEG28-A20FMDV2 (2) was purified by HPLC, formulated in PBS and evaluated in vitro (stability; binding and internalization in αvβ6(+) and αvβ6(-) cells) and in vivo (paired αvβ6(+) and αvβ6(-) xenograft mice: PET/CT, biodistribution, tumor autoradiography and metabolites). Results: The radiotracer 2 was prepared in 90±6 min (incl. formulation; n=3) in 19.3±5.4% decay corrected radiochemical yield (radiochemical purity: >99%; specific activity: 158±36 GBq/μmol) and was stable in PBS and serum (2 h). During in vitro cell binding studies, 2 showed high, αvβ6-targeted binding (αvβ6(+): 42.4±1.2% of total radioactivity, ratio (+)/(-)=8.4/1) and internalization (αvβ6(+): 28.3±0.5% of total radioactivity, (+)/(-)=11.7/1). In vivo, 2 maintained αvβ6-targeted binding (biodistribution; 1 h: αvβ6(+): 1.74±0.38% ID/g, (+)/(-)=2.72/1; 4 h: αvβ6(+): 1.21±0.56% ID/g, (+)/(-)=4.0/1; 11% intact 2 in tumor at 1 h), with highest uptake around the tumor edge (autoradiography). Most of the radioactivity cleared rapidly in the urine within one hour, but a significant fraction remained trapped in the kidneys (4 h: 229±44% ID/g). Conclusion: The Al[18F]/NOTA-based radiolabeling was rapid and efficient, and the radiotracer 2 showed good αvβ6-selectivity in vitro and in vivo. However, in contrast to A20FMDV2 labeled with covalently bound [18F]-prosthetic groups (e.g., [18F]fluorobenzoic acid), 2 demonstrated significant trapping in kidneys, similar to radiometal-labeled chelator-analogs of 2.

KW - Aluminum [18F]fluoride

KW - Fluorine 18

KW - Integrin

KW - NOTA

KW - Peptide

KW - Positron emission tomography

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