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Printing metal-spiked inks for LA-ICP-MS bioimaging internal standardization: comparison of the different nephrotoxic behavior of cisplatin, carboplatin, and oxaliplatin

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Abstract

The study of the distribution of the cytostatic drugs cisplatin, carboplatin, and oxaliplatin along the kidney may help to understand their different nephrotoxic behavior. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) allows the acquisition of trace element images in biological tissues. However, results obtained are affected by several variations concerning the sample matrix and instrumental drifts. In this work, an internal standardization method based on printing an Ir-spiked ink onto the surface of the sample has been developed to evaluate the different distributions and accumulation levels of the aforementioned drugs along the kidney of a rat model. A conventional ink-jet printer was used to print fresh sagittal kidney tissue slices of 4 μm. A reproducible and homogenous deposition of the ink along the tissue was observed. The ink was partially absorbed on top of the tissue. Thus, this approach provides a pseudo-internal standardization, due to the fact that the ablation sample and internal standard take place subsequently and not simultaneously. A satisfactory normalization of LA-ICP-MS bioimages and therefore a reliable comparison of the kidney treated with different Pt-based drugs were achieved even for tissues analyzed on different days. Due to the complete ablation of the sample, the transport of the ablated internal standard and tissue to the inductively coupled plasma-mass spectrometry (ICP-MS) is practically taking place at the same time. Pt accumulation in the kidney was observed in accordance to the dosages administered for each drug. Although the accumulation rate of cisplatin and oxaliplatin is high in both cases, their Pt distributions differ. The strong nephrotoxicity observed for cisplatin and the absence of such side effect in the case of oxaliplatin could explain these distribution differences. The homogeneous distribution of oxaliplatin in the cortical and medullar areas could be related with its higher affinity for cellular transporters such as MATE2-k.

Workflow employed for printing metal-spiked inks in tissue slices and subsequent image standarization using the printed isotope as internal standard

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Acknowledgments

This work was financially supported by the Ministry of Economy and Competitiveness of Spain (CTQ-2011-24585 and CTQ2014-55711-R). The authors want to thank Dr. Heike Traub for her valuable expertise in laser ablation measurements. I. Moraleja also acknowledges Universidad Complutense of Madrid for a predoctoral fellowship.

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    Authors and Affiliations

    1. Analytical Chemistry Department, Universidad Complutense de Madrid, Avda. Complutense s/n, 28040, Madrid, Spain

      Irene Moraleja, M. Luz Mena & M. Milagros Gómez-Gómez

    2. BAM Federal Institute for Materials Research and Testing, Richard-Willstaetter-Str.11, 12489, Berlin, Germany

      Diego Esteban-Fernández & Norbert Jakubowski

    3. Renal Physiopathology Laboratory, Department of Nephrology, Hospital General Universitario Gregorio Marañón, Calle del Dr. Esquerdo, 46, 28007, Madrid, Spain

      Alberto Lázaro, Blanca Humanes & Alberto Tejedor

    4. Proteome Factory AG, Magnusstraße 11, 12489, Berlin, Germany

      Boris Neumann

    5. Charité, Center for Cardiovascular Research, Hessische Str. 3-4, 10115, Berlin, Germany

      Boris Neumann

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    1. Irene Moraleja
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    Irene Moraleja and Diego Esteban-Fernández contributed equally to this work.

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    Moraleja, I., Esteban-Fernández, D., Lázaro, A. et al. Printing metal-spiked inks for LA-ICP-MS bioimaging internal standardization: comparison of the different nephrotoxic behavior of cisplatin, carboplatin, and oxaliplatin. Anal Bioanal Chem 408, 2309–2318 (2016). https://doi.org/10.1007/s00216-016-9327-0

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