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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

Phantom and animal MR imaging study SNR values. SNR values were calculated for a variety of imaging parameters: matrix size (32 × 32, top; 64 × 64, bottom) and slice thickness (x-axis), using 19F MRI in the phantom, bladder and liver. Error bars are the result of 3 ROI image analyses.
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fig0020: Phantom and animal MR imaging study SNR values. SNR values were calculated for a variety of imaging parameters: matrix size (32 × 32, top; 64 × 64, bottom) and slice thickness (x-axis), using 19F MRI in the phantom, bladder and liver. Error bars are the result of 3 ROI image analyses.

Mentions: Another potential reason for the lack of bone uptake observed could be a low signal to noise ratio (SNR). SNR measurements are important in 19F-MRI and provide a measure of sensitivity (i.e. contrast achieved with amount of imaging agent injected). SNR values of a phantom sample with 19F-BP were found to be in the 50–150 range (32 × 32 matrix size) and 15–40 range (64 × 64 matrix size) for different slice thicknesses. The size of the matrix size is indirectly proportional to the sensitivity, hence the higher values obtained at 32 × 32. For the mouse studies these values were found to be in the 10–40 and 2–12 range, and compare favourably to other animal studies from Bible et al. [23] and Giraudeau et al. [24] (Fig. 4). It is important to note, however, that 19F-BP was found to be toxic at concentrations required to achieve in vivo MRI signal (97–119 mM). While other BPs used for nuclear imaging such as 99mTc-MDP are required in micromolar concentrations to obtain image contrast, the amount of BPs required for MRI contrast or therapy is much higher. Toxicity has been observed in animal studies with an amino-bisphosphonate used for therapeutic purposes and injected intravenously (alendronate), at doses of 20 mg/kg. However, doses of 150 mg/kg are required for detecting the 19F-MRI signal of 19F-BP (for a 20 g mouse). Hence, toxicity is likely to be the result of the bisphosphonate and not the trifluoromethyl group, although further studies are required to confirm this. These results prompted us to abandon the study of 19F-BP for bone imaging and look for potential strategies in order to increase its sensitivity.


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)

Phantom and animal MR imaging study SNR values. SNR values were calculated for a variety of imaging parameters: matrix size (32 × 32, top; 64 × 64, bottom) and slice thickness (x-axis), using 19F MRI in the phantom, bladder and liver. Error bars are the result of 3 ROI image analyses.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

fig0020: Phantom and animal MR imaging study SNR values. SNR values were calculated for a variety of imaging parameters: matrix size (32 × 32, top; 64 × 64, bottom) and slice thickness (x-axis), using 19F MRI in the phantom, bladder and liver. Error bars are the result of 3 ROI image analyses.
Mentions: Another potential reason for the lack of bone uptake observed could be a low signal to noise ratio (SNR). SNR measurements are important in 19F-MRI and provide a measure of sensitivity (i.e. contrast achieved with amount of imaging agent injected). SNR values of a phantom sample with 19F-BP were found to be in the 50–150 range (32 × 32 matrix size) and 15–40 range (64 × 64 matrix size) for different slice thicknesses. The size of the matrix size is indirectly proportional to the sensitivity, hence the higher values obtained at 32 × 32. For the mouse studies these values were found to be in the 10–40 and 2–12 range, and compare favourably to other animal studies from Bible et al. [23] and Giraudeau et al. [24] (Fig. 4). It is important to note, however, that 19F-BP was found to be toxic at concentrations required to achieve in vivo MRI signal (97–119 mM). While other BPs used for nuclear imaging such as 99mTc-MDP are required in micromolar concentrations to obtain image contrast, the amount of BPs required for MRI contrast or therapy is much higher. Toxicity has been observed in animal studies with an amino-bisphosphonate used for therapeutic purposes and injected intravenously (alendronate), at doses of 20 mg/kg. However, doses of 150 mg/kg are required for detecting the 19F-MRI signal of 19F-BP (for a 20 g mouse). Hence, toxicity is likely to be the result of the bisphosphonate and not the trifluoromethyl group, although further studies are required to confirm this. These results prompted us to abandon the study of 19F-BP for bone imaging and look for potential strategies in order to increase its sensitivity.

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