Single step 18F-labeling of dimeric cycloRGD for functional PET imaging of tumors in mice

Li, Ying; Liu, Zhibo; Lozada, Jerome; Wong, May Q.; Lin, Kuo-Chi; Yapp, Donald T.; Perrin, David M.

doi:10.1016/j.nucmedbio.2013.08.001

Cited by 33 publications

(30 citation statements)

References 57 publications

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“…Interestingly, in vivo tumor imaging with uptake values were similar to Al-[ 18 F]-NOTA-bisRGD 48 and 10-fold higher values compared to our previous report on a nonfluorescent dimeric cRGD comprising a different linker along with an anionic [ 18 F]-aryl-BF 3 − prosthesis. 46 While it is likely that the rhodamine retarded clearance, more work will be needed to clarify the respective roles that the rhodamine, the zwitterionic AMBF 3 − prosthesis, and the pentaerythritol scaffold play to increase uptake 10-fold.…”

Section: ■ Discussionmentioning

confidence: 99%

Dual Mode Fluorescent ¹⁸F-PET Tracers: Efficient Modular Synthesis of Rhodamine-[cRGD]₂-[¹⁸F]-Organotrifluoroborate, Rapid, and High Yielding One-Step ¹⁸F-Labeling at High Specific Activity, and Correlated in Vivo PET Imaging and ex Vivo Fluorescence

Liu

Radtke

Wong³

et al. 2014

Bioconjugate Chem.

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The design of dual mode fluorescent-PET peptidic tracers that can be labeled with [(18)F]fluoride at high specific activity and high yield has been challenged by the short half-life of (18)F and its aqueous indolence toward nucleophilic displacement, that often necessitates multistep reactions that start with punctiliously dry conditions. Here we present a modular approach to constructing a fluorescent dimeric peptide with a pendant radioprosthesis that is labeled in water with [(18)F]fluoride ion in a single, user-friendly step. The modular approach starts with grafting a new zwitterionic organotrifluoroborate radioprosthesis onto a pentaerythritol core with three pendent alkynes that enable successive grafting of a bright fluorophore (rhodamine) followed by two peptides (cylcoRGD). The construct is labeled with [(18)F]fluoride via isotope exchange within 20 min in a single step at high specific activity (>3 Ci/μmol) and in good yield to provide 275 mCi and high radiochemical purity. Neither drying of the [(18)F]fluoride ion solution nor HPLC purification of the labeled tracer is required. Facile chemical synthesis of this dual mode tracer along with a user-friendly one-step radiolabeling method affords very high specific activity. In vivo PET images of the dual mode tracer are acquired at both high and low specific activities. At very high specific activity, i.e., 3.5 Ci/μmol, tumor uptake is relatively high (5.5%ID/g), yet the associated mass is below the limits of fluorescent detection. At low specific activity, i.e., 0.01 Ci/μmol, tumor uptake in the PET image is reduced by approximately 50% (2.9%ID/g), but the greater associated mass enables fluorescence detection in the tumor. These data highlight a facile production of a dual mode fluorescent-PET tracer which is validated with in vivo and ex vivo images. These data also define critical limitations for the use of dual mode tracers in small animals.

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Section: ■ Discussionmentioning

confidence: 99%

Dual Mode Fluorescent ¹⁸F-PET Tracers: Efficient Modular Synthesis of Rhodamine-[cRGD]₂-[¹⁸F]-Organotrifluoroborate, Rapid, and High Yielding One-Step ¹⁸F-Labeling at High Specific Activity, and Correlated in Vivo PET Imaging and ex Vivo Fluorescence

Liu

Radtke

Wong³

et al. 2014

Bioconjugate Chem.

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“…reported the usage of arylborimidine 22 as the precursor for 18 F-labeling of dimeric-cylcoRGD ( 23 ; Figure 4D). [21] From a distinct mechanistic point of view, [18 F]trifluorborate based labeling reagents could also be obtained through isotopic exchange with 19 F-trifluorborates. These authors also conducted a kit-like 18 F-labeling strategy for RGD peptide where RGD–ArBF 3 ( 24 ) was reacted with fluorine-18 in acidic conditions (Figure 5A).…”

Section: Direct Methods For 18f-labeling Of Biomoleculesmentioning

confidence: 99%

¹⁸F‐Labeling of Sensitive Biomolecules for Positron Emission Tomography

Krishnan

Vasdev

et al. 2017

Chemistry A European J

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Positron emission tomography (PET) imaging study of fluorine-18 labeled biomolecules is an emerging and rapidly growing area for preclinical and clinical research. The present review focuses on recent advances in radiochemical methods for incorporating fluorine-18 into biomolecules via ‘direct’ or ‘indirect’ bioconjugation. Recently developed prosthetic groups and pre-targeting strategies, as well as representative examples in 18F-labeling of biomolecules in PET imaging research studies are highlighted.

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“…Current strategies for the direct labelling of peptides have used fluoride‐sequestering strategies. Radiolabelled trifluoroborates14 have been prepared using aqueous [ 18 F]fluoride and KFH 2 , but at low pH values (pH 2), while aluminum hydroxide complexes16 require heating at elevated temperatures (105 °C) for fluorination. A silicon‐based fluoride‐acceptor approach15 and direct nucleophilic fluorination reactions17, 18 at a carbon center require anhydrous conditions and heating to incorporate fluoride substituents.…”

Section: Methodsmentioning

confidence: 99%

A Localized Tolerance in the Substrate Specificity of the Fluorinase Enzyme enables “Last‐Step” ¹⁸F Fluorination of a RGD Peptide under Ambient Aqueous Conditions

et al. 2014

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A strategy for last‐step 18F fluorination of bioconjugated peptides is reported that exploits an “Achilles heel” in the substrate specificity of the fluorinase enzyme. An acetylene functionality at the C‐2 position of the adenosine substrate projects from the active site into the solvent. The fluorinase catalyzes a transhalogenation of 5′‐chlorodeoxy‐2‐ethynyladenosine (ClDEA) to 5′‐fluorodeoxy‐2‐ethynyladenosine (FDEA). Extending a polyethylene glycol linker from the terminus of the acetylene allows the presentation of bioconjugation cargo to the enzyme for 18F labelling. The method uses an aqueous solution (H218O) of [18F]fluoride generated by the cyclotron and has the capacity to isotopically label peptides of choice for positron emission tomography (PET).

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Single step 18F-labeling of dimeric cycloRGD for functional PET imaging of tumors in mice

Cited by 33 publications

References 57 publications

Dual Mode Fluorescent ¹⁸F-PET Tracers: Efficient Modular Synthesis of Rhodamine-[cRGD]₂-[¹⁸F]-Organotrifluoroborate, Rapid, and High Yielding One-Step ¹⁸F-Labeling at High Specific Activity, and Correlated in Vivo PET Imaging and ex Vivo Fluorescence

Dual Mode Fluorescent ¹⁸F-PET Tracers: Efficient Modular Synthesis of Rhodamine-[cRGD]₂-[¹⁸F]-Organotrifluoroborate, Rapid, and High Yielding One-Step ¹⁸F-Labeling at High Specific Activity, and Correlated in Vivo PET Imaging and ex Vivo Fluorescence

¹⁸F‐Labeling of Sensitive Biomolecules for Positron Emission Tomography

A Localized Tolerance in the Substrate Specificity of the Fluorinase Enzyme enables “Last‐Step” ¹⁸F Fluorination of a RGD Peptide under Ambient Aqueous Conditions

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Single step 18F-labeling of dimeric cycloRGD for functional PET imaging of tumors in mice

Cited by 33 publications

References 57 publications

Dual Mode Fluorescent 18F-PET Tracers: Efficient Modular Synthesis of Rhodamine-[cRGD]2-[18F]-Organotrifluoroborate, Rapid, and High Yielding One-Step 18F-Labeling at High Specific Activity, and Correlated in Vivo PET Imaging and ex Vivo Fluorescence

Dual Mode Fluorescent 18F-PET Tracers: Efficient Modular Synthesis of Rhodamine-[cRGD]2-[18F]-Organotrifluoroborate, Rapid, and High Yielding One-Step 18F-Labeling at High Specific Activity, and Correlated in Vivo PET Imaging and ex Vivo Fluorescence

18F‐Labeling of Sensitive Biomolecules for Positron Emission Tomography

A Localized Tolerance in the Substrate Specificity of the Fluorinase Enzyme enables “Last‐Step” 18F Fluorination of a RGD Peptide under Ambient Aqueous Conditions

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Dual Mode Fluorescent ¹⁸F-PET Tracers: Efficient Modular Synthesis of Rhodamine-[cRGD]₂-[¹⁸F]-Organotrifluoroborate, Rapid, and High Yielding One-Step ¹⁸F-Labeling at High Specific Activity, and Correlated in Vivo PET Imaging and ex Vivo Fluorescence

Dual Mode Fluorescent ¹⁸F-PET Tracers: Efficient Modular Synthesis of Rhodamine-[cRGD]₂-[¹⁸F]-Organotrifluoroborate, Rapid, and High Yielding One-Step ¹⁸F-Labeling at High Specific Activity, and Correlated in Vivo PET Imaging and ex Vivo Fluorescence

¹⁸F‐Labeling of Sensitive Biomolecules for Positron Emission Tomography

A Localized Tolerance in the Substrate Specificity of the Fluorinase Enzyme enables “Last‐Step” ¹⁸F Fluorination of a RGD Peptide under Ambient Aqueous Conditions