title: Printing metal-spiked inks for LA-ICP-MS bioimaging internal standardization: comparison of the different nephrotoxic behavior of cisplatin, carboplatin, and oxaliplatin.
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.
authors.affiliation: Analytical Chemistry Department, Universidad Complutense de Madrid, Avda. Complutense s/n, 28040, Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Moraleja
authors.affiliation: BAM Federal Institute for Materials Research and Testing, Richard-Willstaetter-Str.11, 12489, Berlin, Germany. diego.esteban-fernandez@bam.de.
authors.forename: Diego
authors.initials: D
authors.lastname: Esteban-Fernández
authors.affiliation: Renal Physiopathology Laboratory, Department of Nephrology, Hospital General Universitario Gregorio Marañón, Calle del Dr. Esquerdo, 46, 28007, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Lázaro
authors.affiliation: Renal Physiopathology Laboratory, Department of Nephrology, Hospital General Universitario Gregorio Marañón, Calle del Dr. Esquerdo, 46, 28007, Madrid, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Humanes
authors.affiliation: Proteome Factory AG, Magnusstraße 11, 12489, Berlin, Germany.|Charité, Center for Cardiovascular Research, Hessische Str. 3-4, 10115, Berlin, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Neumann
authors.affiliation: Renal Physiopathology Laboratory, Department of Nephrology, Hospital General Universitario Gregorio Marañón, Calle del Dr. Esquerdo, 46, 28007, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Tejedor
authors.affiliation: Analytical Chemistry Department, Universidad Complutense de Madrid, Avda. Complutense s/n, 28040, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Luz Mena
authors.affiliation: BAM Federal Institute for Materials Research and Testing, Richard-Willstaetter-Str.11, 12489, Berlin, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Jakubowski
authors.affiliation: Analytical Chemistry Department, Universidad Complutense de Madrid, Avda. Complutense s/n, 28040, Madrid, Spain.
authors.forename: M Milagros
authors.initials: MM
authors.lastname: Gómez-Gómez
mesh_terms: D000818:Animals; D016190:Carboplatin / Q000378:metabolism / Q000633:toxicity*; D002945:Cisplatin / Q000378:metabolism / Q000633:toxicity*; D007281:Ink; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000378:metabolism / Q000633:toxicity*; D000077150:Oxaliplatin; D011327:Printing; D051381:Rats; D012015:Reference Standards
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D016190:Carboplatin; D002945:Cisplatin
keywords: Bioimaging; LA-ICP-MS; Nephrotoxicity; Printed internal standard; Pt-based drugs