A bone imaging toolkit of 21 fluorescent probes with variable spectroscopic properties, bone mineral binding affinities, and antiprenylation activities has been created, including a novel linking strategy. The linking chemistry allows attachment of a diverse selection of dyes fluorescent in the visible to near-infrared range to any of the three clinically important heterocyclic bisphosphonate bone drugs (risedronate, zoledronate, and minodronate or their analogues). The resultant suite of conjugates offers multiple options to "mix and match" parent drug structure, fluorescence emission wavelength, relative bone affinity, and presence or absence of antiprenylation activity, for bone-related imaging applications.
Compounds 1a–1c were gifts from Warner Chilcott Pharmaceuticals (formerly Procter & Gamble Pharmaceuticals). This work was supported by the University of Southern California and in part by NIH grants 1R01DC009837, 1R21DE023410, 1R43AR067021-01A1, and 1R43DE025524-01. A.J.R. and F.P.C. acknowledge support from Warner Chilcott. J.D. was supported through funding from the Oxford NIHR Biomedical Research Unit.
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- School of Medicine, Medical Sciences & Nutrition, Medical Sciences - Senior Lecturer
- School of Medicine, Medical Sciences & Nutrition, MRC/Versus Arthritis Centre for Musculoskeletal Health and Work
- School of Medicine, Medical Sciences & Nutrition, Molecular and Cellular Function
- School of Medicine, Medical Sciences & Nutrition, Institute of Medical Sciences
- School of Medicine, Medical Sciences & Nutrition, Aberdeen Centre for Arthritis and Musculoskeletal Health (ACAMH)