Page 13 - Shimadzu Journal vol.3 Issue3

Interview

The Challenge of Discovery and Development of Pharmaceutical
Products Using Imaging Mass Spectrometry: iMScope TRIO

Imaging mass spectrometry (IMS), which uses MALDI-TOF/MS analysis to identify the presence of target substances in
biosamples such as tissue samples, is a cutting-edge measurement technology that is becoming increasingly popular
in medical and biological research. The technology has potential not only for drug delivery and pharmacokinetics
research, but also as a useful tool in biomarker research, and increasing numbers of measurements are now carried
out using the iMScope TRIO. We sat down with Hidefumi Kaji, PhD, of Mitsubishi Tanabe Pharma Corporation’s
DMPK (Drug Metabolism and Pharmacokinetics) Research Laboratories, Research Division, and asked him about his
use of this technology.
Hidefumi Kaji, Ph D
*Affiliates and titles of the interviewee are current as of the time of reporting. Group Manager
DMPK Research Laboratories, Research Division
Mitsubishi Tanabe Pharma Corporation

Introduction actually uses the instrument would be delighted by this. It is
extremely important to position accurately and understand what part
You have been using the iMScope TRIO at the laboratory in
of the sample slice is being analyzed. The higher the resolution, the
Shimadzu’s Sanjo Works for around two and a half years. What more likely it is that, just by moving five or ten microns, we are
sort of research is it mainly used in? looking at a completely different place. The use of IMS has made it
I work in the DMPK Research Laboratories, and am engaged mainly possible to confirm the specific distribution of the compound under
in the creation of pharmaceutical products, specifically the area of evaluation within retinal melanin at super-high resolution, down to
preclinical DMPK. In my work, I aim to use the iMScope TRIO to five microns. Many people have been amazed that we are able to
examine the distribution of pharmaceutical candidate compounds in examine samples in such detail. When people see the iMScope TRIO’s
animal organs and tissue, and evaluate fluctuations in endogenous high-resolution analysis in action for the first time, the impact is
substances, biomarkers, and so on. enormous.

Pharmacokinetic Analysis of Low Molecular Weight
Compounds (1)
Could you please give us an actual example of pharmacokinetic
analysis?
Of course. We used the iMScope TRIO to evaluate the distribution of
a certain low molecular weight compound in rats. The compound we
used is characterized by the fact that it bonds specifically to, and
accumulate, the melanin in the eyeball. If a compound under
development builds up by bonding to melanin or in some other way,
Pharmacokinetic Analysis of Low Molecular Weight
we need to be careful about the photosensitivity of the compound.
However, it’s not always the case that if a compound bonds with Compounds (2)
melanin and is distributed within it, it demonstrates toxicity when it Are there any other examples you can give us?
decomposes as a result of photosensitivity. Such understanding of
what sort of degradation product occurs as a result of light is There is a substance called gentamycin, which is known to express
important in predicting the risk of toxicity. Furthermore, if we can toxicity within the kidneys in rats. There have been few reports that
establish that a compound dissipates relatively quickly, it usually have proven where within the kidney it is distributed and expresses
means there will be no problems. From the pharmacokinetic toxicity, and so we looked at whether it is possible to use IMS
standpoint, it is very important in the creation of safe drugs that we technology to evaluate this. Specifically, we implemented verification
ascertain a compound’s profile at an early stage of development, to using 10-micron super-high-resolution analysis. Results showed that,
see if it bonds to and accumulate melanin and what degradation when we looked at the distribution of the compound at a resolution
products might occur. that allowed the recognition of proximal tubules and glomerulus,
gentamycin was distributed in proximal tubules, but had not built up
in almost any other areas. In other words, we were able to confirm
that the buildup of gentamycin in proximal tubules is the mechanism
iMScope TRIO was its spatial resolution.
for toxicity expression.
That’s right. The instrument is characterized by having a microscope
at the front. The laser spec has improved significantly in the past few
Did you get more insightful analysis results thanks to using this
years, meaning that we can now perform high-resolution analysis, technology?
but I think that when analyzing a sample slice, the key point is being
able to ascertain what point on the sample was being measured Well, we’re still at the basic research level, but we analyze biomarker
when the image in question was obtained. Having a microscope fluctuation, which tells us what endogenous substances are active in
means that we can observe a part in detail and match results with a particular pathology caused by administration of a compound. For
what we are actually measuring. This has allowed us to correctly example, if gentamycin is administered and causes a disorder, it is
analyze at super-high resolution for the first time. Anyone who assumed that the concentration of a particular endogenous

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