Limits...
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 molecular structure of 3 (CCDC ID 960161).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4834630&req=5

fig0005: The molecular structure of 3 (CCDC ID 960161).

Mentions: The reaction scheme for the synthesis of 19F-BP is shown in Scheme 1. Tetraethyl aminomethyl-bisphosphonate (2) was synthesized following published methods [20], [21]. Briefly, diethyl phosphite, triethylorthoformate and dibenzylamine were reacted for 29 h at 150–160 °C to yield the benzylated bisphosphonate (1). The amino group of 1 was deprotected with H2 and 10% Pd/C catalyst to yield 2. After removal of the catalyst, 2 was reacted with 2.9 equivalents of trifluoroacetic anhydride (TFAA) in dry DCM for 3 h. Excess TFAA was used in order to prevent low reaction yields due to potential hydrolysis of the anhydride. After evaporation of the volatiles and work-up, 3 was recrystallised from cold hexanes in good yields (78%). The compound was characterised by NMR, HR-MS and the structure confirmed by X-ray crystallography (Fig. 1 and Fig. SI)


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 molecular structure of 3 (CCDC ID 960161).
© Copyright Policy - CC BY
Related In: Results  -  Collection

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

fig0005: The molecular structure of 3 (CCDC ID 960161).
Mentions: The reaction scheme for the synthesis of 19F-BP is shown in Scheme 1. Tetraethyl aminomethyl-bisphosphonate (2) was synthesized following published methods [20], [21]. Briefly, diethyl phosphite, triethylorthoformate and dibenzylamine were reacted for 29 h at 150–160 °C to yield the benzylated bisphosphonate (1). The amino group of 1 was deprotected with H2 and 10% Pd/C catalyst to yield 2. After removal of the catalyst, 2 was reacted with 2.9 equivalents of trifluoroacetic anhydride (TFAA) in dry DCM for 3 h. Excess TFAA was used in order to prevent low reaction yields due to potential hydrolysis of the anhydride. After evaporation of the volatiles and work-up, 3 was recrystallised from cold hexanes in good yields (78%). The compound was characterised by NMR, HR-MS and the structure confirmed by X-ray crystallography (Fig. 1 and Fig. SI)

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