Direct molecular analysis of whole-body animal tissue sections by imaging MALDI mass spectrometry.
Imaging mass spectrometry (IMS) that utilizes matrix-assisted laser desorption/ionization (MALDI) technology can provide a molecular ex vivo view of resected organs or whole-body sections from an animal, making possible the label-free tracking of both endogenous and exogenous compounds with spatial resolution and molecular specificity. Drug distribution and, for the first time, individual metabolite distributions within whole-body tissue sections can be detected simultaneously at various time points following drug administration. IMS analysis of tissues from 8 mg/kg olanzapine dosed rats revealed temporal distribution of the drug and metabolites that correlate to previous quantitative whole-body autoradiography studies. Whole-body MALDI IMS is further extended to detecting proteins from organs present in a whole-body sagittal tissue section. This technology will significantly help advance the analysis of novel therapeutics and may provide deeper insight into therapeutic and toxicological processes, revealing at the molecular level the cause of efficacy or side effects often associated with drug administration.
Khatib-Shahidi
Sheerin
S
Mass Spectrometry Research Center, Departments of Chemistry and Biochemistry, Vanderbilt University, 465 21st Avenue S, Suite 9160 MRB III, Nashville, Tennessee 37221, USA.
Andersson
Malin
M
Herman
Jennifer L
JL
Gillespie
Todd A
TA
Caprioli
Richard M
RM
D000818:Animals; D014150:Antipsychotic Agents / Q000493:pharmacokinetics; D001569:Benzodiazepines / Q000493:pharmacokinetics; D001923:Brain Chemistry; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis; D000077152:Olanzapine; D011506:Proteins / Q000032:analysis*; D051381:Rats; D011916:Rats, Inbred F344; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D046888:Tissue Array Analysis / Q000379:methods*
D014150:Antipsychotic Agents; D009419:Nerve Tissue Proteins; D011506:Proteins; D001569:Benzodiazepines; D000077152:Olanzapine