Abstract A114: Quantitative mass spectrometry imaging: A game changer in the pharmaceutical industry

Abstract

Abstract Developing a drug requires to demonstrate its efficacy in preclinical and clinical studies but also to characterize its pharmacokinetics properties. If Quantitative Whole-Body Autoradiography (QWBA) is still a gold standard to support the design of radiolabelled clinical studies, its lack of molecular specificity limits the understanding of the distribution of the drug and its metabolites, with no establishing of separate quantitative results for each target tissue of interest. On the contrary, the use of high resolution mass spectrometers such as FT-ICR MS allows a quantitative characterization of the metabolic profile of the drug at the tissue level in order to further understand its behaviour in the organism. A comparative analysis between QWBA and QMSI was applied as a complementary approach to follow chloroquine and one of its metabolites (desethyl-chloroquine) at different time-points after a single administration of a radiolabeled dose to Long-Evans male rats (30 mg/kg). 1H-Chloroquine and 1H-desethyl chloroquine were well detected by MALDI-FTICR in the eye including; the uveal tract, the vitreous humor, the lens and the Harderian gland. In the mid whole-body region, both compounds were also detected in various organs from the unique prepared T4h sections. Interestingly the two compounds were co-localized into the tissue sections and their distributions matched the zones obtained by QWBA. In QWBA additional regions containing the radiolabeled moiety could be clearly identified because of the high sensitivity of the technique. The advantage brought by MALDI QMSI was the ability to discriminate between parent drug 1H-choloroquine and its metabolite 1H-desethyl chloroquine so that each compound had its own distribution image and thus its own quantification data directly in one tissue section. The used labeled forms of both compounds during the matrix deposit allowed normalizing the data for each position targeted with the MALDI onto the section of interest and the calibration range of both 1H-choloroquine and 1H-desethyl chloroquine and quantifying each compound into the organs of interest with the ILC approach. Finally the QMSI was able to demonstrate the disappearance of the drug and its metabolite with time to better understand differential pharmacokinetics analysis demonstrating the additional input of the technology compared to QWBA. Citation Format: Rima Ait-Belkacem, Guillaume Hochart, Joseph Marini, Aurore Tomezyk, p Mantefeul, B. Jung, David Bonnel, Don Mc Kenzie, Jonathan Stauber. Quantitative mass spectrometry imaging: A game changer in the pharmaceutical industry [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A114. doi:10.1158/1535-7163.TARG-19-A114