Publications

@article{McCrorie2022-ls,

title = {Detection of label-free drugs within brain tissue using orbitrap 

 secondary ion mass spectrometry as a complement to 

 neuro-oncological drug delivery},

author = {Phoebe McCrorie and Jonathan Rowlinson and David J Scurr and Maria Marlow and Ruman Rahman},

year  = {2022},

date = {2022-03-01},

journal = {Pharmaceutics},

volume = {14},

number = {3},

pages = {571},

publisher = {MDPI AG},

abstract = {Historically, pre-clinical neuro-oncological drug delivery 

 studies have exhaustively relied upon overall animal survival as 

 an exclusive measure of efficacy. However, with no adopted 

 methodology to both image and quantitate brain parenchyma 

 penetration of label-free drugs, an absence of efficacy 

 typically hampers clinical translational potential, rather than 

 encourage re-formulation of drug compounds using nanocarriers to 

 achieve greater tissue penetration. OrbiSIMS, a next-generation 

 analytical instrument for label-free imaging, combines the high 

 resolving power of an OrbiTrapTM mass spectrometer with the 

 relatively high spatial resolution of secondary ion mass 

 spectrometry. Here, we develop an ex vivo pipeline using 

 OrbiSIMS to accurately detect brain penetration of drug 

 compounds. Secondary ion spectra were acquired for a panel of 

 drugs (etoposide, olaparib, gemcitabine, vorinostat and 

 dasatinib) under preclinical consideration for the treatment of 

 isocitrate dehydrogenase-1 wild-type glioblastoma. Each drug 

 demonstrated diagnostic secondary ions (all present molecular 

 ions [M-H]− which could be discriminated from brain analytes 

 when spiked at \>20 µg/mg tissue. Olaparib/dasatinib and 

 olaparib/etoposide dual combinations are shown as exemplars for 

 the capability of OrbiSIMS to discriminate distinct drug ions 

 simultaneously. Furthermore, we demonstrate the imaging 

 capability of OrbiSIMS to simultaneously illustrate label-free 

 drug location and brain chemistry. Our work encourages the 

 neuro-oncology community to consider mass spectrometry imaging 

 modalities to complement in vivo efficacy studies, as an 

 analytical tool to assess brain distribution of systemically 

 administered drugs, or localised brain penetration of drugs 

 released from micro- or nano-scale biomaterials.},

keywords = {Drug delivery, Glioblastoma, mass spectrometry imaging, OrbiSIMS},

pubstate = {published},

tppubtype = {article}

}