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A bisphosphonate for (19)F-magnetic resonance imaging.

Kenny GD, Shaw KP, Sivachelvam S, White AJ, Botnar RM, T M de Rosales R - J Fluor Chem (2016)

Bottom Line: The potential of (19)F-BP to provide contrast was analysed in vitro and in vivo using (19)F-MRI.The preliminary in vivo MRI study reported here allowed us to visualise the biodistribution of (19)F-BP, showing uptake in the liver and in the bladder/urinary system areas.However, bone uptake was not observed.

View Article: PubMed Central - PubMed

Affiliation: Division of Imaging Sciences & Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, UK.

ABSTRACT

(19)F-magnetic resonance imaging (MRI) is a promising technique that may allow us to measure the concentration of exogenous fluorinated imaging probes quantitatively in vivo. Here, we describe the synthesis and characterisation of a novel geminal bisphosphonate ((19)F-BP) that contains chemically-equivalent fluorine atoms that show a single and narrow (19)F resonance and a bisphosphonate group that may be used for labelling inorganic materials based in calcium phosphates and metal oxides. The potential of (19)F-BP to provide contrast was analysed in vitro and in vivo using (19)F-MRI. In vitro studies demonstrated the potential of (19)F-BP as an MRI contrast agent in the millimolar concentration range with signal-to-noise ratios (SNR) comparable to previously reported fluorinated probes. The preliminary in vivo MRI study reported here allowed us to visualise the biodistribution of (19)F-BP, showing uptake in the liver and in the bladder/urinary system areas. However, bone uptake was not observed. In addition, (19)F-BP showed undesirable toxicity effects in mice that prevent further studies with this compound at the required concentrations for MRI contrast. This study highlights the importance of developing (19)F MRI probes with the highest signal intensity achievable.

No MeSH data available.


Related in: MedlinePlus

The synthetic scheme of 19F-BP. (i) 29 h at 150–160 °C; (ii) H2, 10% Pd/C catalyst in EtOH, room temperature; (iii) 3 h in dry DCM; (iv) (a) 24 h, Me3SiBr (15 eq) in dry DCM, room temperature (b) 1.5 h MeOH, 1.5 mL, room temperature.
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fig0025: The synthetic scheme of 19F-BP. (i) 29 h at 150–160 °C; (ii) H2, 10% Pd/C catalyst in EtOH, room temperature; (iii) 3 h in dry DCM; (iv) (a) 24 h, Me3SiBr (15 eq) in dry DCM, room temperature (b) 1.5 h MeOH, 1.5 mL, room temperature.

Mentions: We are interested in developing 19F-MRI contrast agents for molecular imaging that show single and narrow 19F resonances and short T1 relaxation times. Previously we have shown that 1,1-bisphosphonates (BPs) bind very strongly to metabolically active bone and calcium phosphate materials such as hydroxyapatite using SPECT and PET imaging [16], [17], [18], [19]. In addition, we found that BPs also bind very strongly to many nanomaterials based on lanthanide metal oxides of the type M2O3 (M = Gd, Er, among others) with known relaxation rate-enhancement properties [19]. We hypothesised that a fluorinated BP molecule could be an useful tool in the development of 19F-MRI probes, that would allow to combine of the amplification properties of nanoparticle-based platforms (high numbers of equivalent fluorine atoms) with the relaxation-enhancement properties of lanthanide-based materials (short acquisition times) without affecting their water solubility. In this way we could potentially achieve 19F-MRI probes with high signal intensity and sensitivity that could be imaged in a short time. In addition, their solution and in vivo properties could be easily controlled by surface modification using the same BP chemistry. In this work, we report our first attempts at achieving this aim by synthesizing and characterising a new fluorinated BP (19F-BP, Scheme 1) and evaluate for the first time its properties as a single molecule for 19F-MRI in vitro and in vivo.


A bisphosphonate for (19)F-magnetic resonance imaging.

Kenny GD, Shaw KP, Sivachelvam S, White AJ, Botnar RM, T M de Rosales R - J Fluor Chem (2016)

The synthetic scheme of 19F-BP. (i) 29 h at 150–160 °C; (ii) H2, 10% Pd/C catalyst in EtOH, room temperature; (iii) 3 h in dry DCM; (iv) (a) 24 h, Me3SiBr (15 eq) in dry DCM, room temperature (b) 1.5 h MeOH, 1.5 mL, room temperature.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834630&req=5

fig0025: The synthetic scheme of 19F-BP. (i) 29 h at 150–160 °C; (ii) H2, 10% Pd/C catalyst in EtOH, room temperature; (iii) 3 h in dry DCM; (iv) (a) 24 h, Me3SiBr (15 eq) in dry DCM, room temperature (b) 1.5 h MeOH, 1.5 mL, room temperature.
Mentions: We are interested in developing 19F-MRI contrast agents for molecular imaging that show single and narrow 19F resonances and short T1 relaxation times. Previously we have shown that 1,1-bisphosphonates (BPs) bind very strongly to metabolically active bone and calcium phosphate materials such as hydroxyapatite using SPECT and PET imaging [16], [17], [18], [19]. In addition, we found that BPs also bind very strongly to many nanomaterials based on lanthanide metal oxides of the type M2O3 (M = Gd, Er, among others) with known relaxation rate-enhancement properties [19]. We hypothesised that a fluorinated BP molecule could be an useful tool in the development of 19F-MRI probes, that would allow to combine of the amplification properties of nanoparticle-based platforms (high numbers of equivalent fluorine atoms) with the relaxation-enhancement properties of lanthanide-based materials (short acquisition times) without affecting their water solubility. In this way we could potentially achieve 19F-MRI probes with high signal intensity and sensitivity that could be imaged in a short time. In addition, their solution and in vivo properties could be easily controlled by surface modification using the same BP chemistry. In this work, we report our first attempts at achieving this aim by synthesizing and characterising a new fluorinated BP (19F-BP, Scheme 1) and evaluate for the first time its properties as a single molecule for 19F-MRI in vitro and in vivo.

Bottom Line: The potential of (19)F-BP to provide contrast was analysed in vitro and in vivo using (19)F-MRI.The preliminary in vivo MRI study reported here allowed us to visualise the biodistribution of (19)F-BP, showing uptake in the liver and in the bladder/urinary system areas.However, bone uptake was not observed.

View Article: PubMed Central - PubMed

Affiliation: Division of Imaging Sciences & Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, UK.

ABSTRACT

(19)F-magnetic resonance imaging (MRI) is a promising technique that may allow us to measure the concentration of exogenous fluorinated imaging probes quantitatively in vivo. Here, we describe the synthesis and characterisation of a novel geminal bisphosphonate ((19)F-BP) that contains chemically-equivalent fluorine atoms that show a single and narrow (19)F resonance and a bisphosphonate group that may be used for labelling inorganic materials based in calcium phosphates and metal oxides. The potential of (19)F-BP to provide contrast was analysed in vitro and in vivo using (19)F-MRI. In vitro studies demonstrated the potential of (19)F-BP as an MRI contrast agent in the millimolar concentration range with signal-to-noise ratios (SNR) comparable to previously reported fluorinated probes. The preliminary in vivo MRI study reported here allowed us to visualise the biodistribution of (19)F-BP, showing uptake in the liver and in the bladder/urinary system areas. However, bone uptake was not observed. In addition, (19)F-BP showed undesirable toxicity effects in mice that prevent further studies with this compound at the required concentrations for MRI contrast. This study highlights the importance of developing (19)F MRI probes with the highest signal intensity achievable.

No MeSH data available.


Related in: MedlinePlus