Nominee: Lavinia Morosi – Clinical Cancer Pharmacology Unit, Department of Oncology, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri" (Milan, Italy)
Nominated By: Massimo Zucchetti Head of Clinical Cancer Pharmacology Unit, Department of Oncology, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri" (Milan, Italy)
Supporting Comments: Dr Lavinia Morosi is a young researcher employed in our laboratory since May 2012. She is highly motivated to do high quality research in the field of bioanalysis, to be applied to pre-clinical and clinical pharmacology studies. She is certainly brilliant and competent in her experimental work and her work is fundamental for our projects.
The main aspect of the activities of Dr Morosi is related to the use of HPLC, LC-MS/MS and MALDI Imaging techniques. Including sample manipulation and extraction (i.e. by solvent or automated SPE), developing and validation of HPLC analytical methods under GLP conditions to measure small molecule, mainly new anticancer agent in different biological specimens, both at preclinical and clinical level. The most peculiar part of her work includes the development of mass spectrometry imaging techniques able to visualize the distribution of small molecules into tissues. In particular, she is one of the youngest researchers to have implemented the use of MSI technology in the field of cancer pharmacology (see ref No 5). The analysis of anti cancer drugs distribution within the neoplastic tissue highlighted that it is mainly heterogeneous and scarce and that is a probable cause of drug resistance.
What made you choose a career in bioanalysis?
I choose a career in bioanalysis because I think that to understand the complex biological processes that are involved in development of diseases or response to therapy the availability of accurate methods to measure the various parameter of interest is fundamental. Purely descriptive or qualitative analysis is important, but for a deeper and more objective knowledge new analytical methods and the research of new techniques are always indispensable.
Describe the main highlights of your bioanalytical research, and its importance to the bioanalytical community.
A complete penetration of anticancer drugs in solid tumors is essential to obtain an optimal therapeutic effect, but analysis and quantification of administered drugs relies mainly on LC–MS/MS in plasma or tissue homogenate. This method approaches every tissue and organ as a homogeneous component ignoring the heterogeneity of tumor tissue and the consequent irregular drug perfusion. The developing of technologies to obtain a deeper knowledge of drug tumor distribution is fundamental. In this field, imaging mass spectrometry (MSI) has great potentialities giving the capacity to visualize drug distribution in tissues with a optimal spatial resolution and specificity.
I have developed a MSI protocol, based on TiO2 nanoparticles, which allow us to perform analysis of paclitaxel (PTX), an anticancer drug to study its distribution inside tissues. The heterogeneous drug penetration in different tumor model is evident from the MALDI imaging results. The differences between the various models do not always relate to significant changes in drug content in tumor homogenate examined by classical HPLC analysis. The specificity of the method clarifies the heterogeneity of the drug distribution that is analyzed from a quantitative point of view too, highlighting how marked are the variations of paclitaxel amounts in different part of tumors.
What is the impact of your work beyond your home laboratory?
The MSI method that I developed to visualize paclitaxel in tissues was implemented in a clinical project in which our laboratory was involved in the pharmacokinetic study. We assessed the paclitaxel penetration in peritoneal wall samples from patients affected by ovarian cancer with peritoneal carcinomatosis that underwent hyperthermic intraperitoneal chemotherapy (HIPEC). The drug was present only in the portion of tissue in contact with the perfusate fluid in the peritoneal cavity, and was not detectable in the deeper layers. PTX penetrated up to 0.5 mm on average in peritoneal tissue. These data support the view that HIPEC should be employed only when no residual macroscopic disease or tumor deposits are present after surgery.
Describe the most difficult challenge you have encountered in the laboratory and how you overcame it.
The MALDI MSI analysis of heterogeneous tissues such as tumors is challenging mostly because of the ion suppression effect that may be different in the various parts of the tumor section. The ion suppression effect is mainly due to endogenous species (e.g. lipids) competing for ionization or to salts accumulation typical of biological tissue, and this process can cause the generation of artifacts. I overcame this problem using a normalization approach based on a reference molecule (deuterated paclitaxel) sprayed on the tissue and used as reference ion. Normalization ensures that the irregular drug distribution of PTX in the tumor section is real and not caused by different ion suppression effects in different parts of the tumor. Normalization moreover, improves the quality of the image, reducing irregularities and variability inside each spot.
Describe your role in bioanalytical communities/groups.
My experience in inter-disciplinary group is related to my work on nanoparticles carriers for hydrophobic anticancer drugs. In this field I collaborated with chemical engineers from Politecnico di Milano to develop and characterize polymeric carriers and with preclinical model experts to test pharmacokinetic properties and antitumor activity of the drug loaded nanoparticles.
Moreover we collaborate actively with bioinformatics from Mach Foundation in Trento in the development of automated method to elaborate and analyze MALDI images in order to describe and compare distribution of molecules of interest.
Please list up to five of your publications in the field of bioanalysis:
- Cesca M, Morosi L, Berndt A, Fuso Nerini I, Frapolli R, Richter P, Decio A, Dirsch O, Micotti E, Giordano S, D’Incalci M, Davoli E, Zucchetti M, Giavazzi R. Bevacizumab-induced inhibition of angiogenesis promotes a more homogeneous intratumoral distribution of paclitaxel, improving the antitumor response. Mol Cancer Ther. doi: 10.1158/1535-7163 (2015).
- Colombo C, Morosi L, Bello E, Ferrari R, Licandro SA, Lupi M, Ubezio P, Morbidelli M, Zucchetti M, D’Incalci M, Moscatelli D, Frapolli R. PEGylated Nanoparticles Obtained through Emulsion Polymerization as Paclitaxel Carriers. Mol Pharm. 13(1), 40–46 (2016)
- Ansaloni L, Coccolini F, Morosi L, Ballerini A, Ceresoli M, Grosso G, Bertoli P, Busci LM, Lotti M, Cambria F, Pisano M, Rossetti D, Frigerio L, D’Incalci M, Zucchetti M. Pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer. Br J Cancer. 112(2), 306–12(2015).
- Morosi L, Spinelli P, Zucchetti M, Pretto F, Carrà A, D’Incalci M, Giavazzi R, Davoli E. Determination of paclitaxel distribution in solid tumors by nano-particle assisted laser desorption ionization mass spectrometry imaging. PLoS One. 8(8), e72532 (2013).
- Morosi L, Zucchetti M, D’Incalci M, Davoli E. Imaging mass spectrometry: challenges in visualization of drug distribution in solid tumors. Curr Opin Pharmacol.13(5), 807–812 (2013).
Please select one publication from above that best highlights your career to date in the field of bioanalysis and provide an explanation for your choice.
I choose the publication on PlosOne (4) about “Determination of paclitaxel distribution in solid tumors by nano-particle assisted laser desorption ionization mass spectrometry imaging”, because it is my first work on mass spectrometry imaging and it present an innovative, simple and reproducible method to analyze the distribution in tissue from treated animals of a widely used anticancer drug.
Find out more about this year’s New Investigator Award, the prize, the judging panel and the rest of our nominees.