Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs

Riccardo Zecchi, Pietro Franceschi, Laura Tigli, Francesca Ricci, Francesca Boscaro, Barbara Pioselli, Valentina Mileo, Xabier Murgia, Federico Bianco, Fabrizio Salomone, Augusto F. Schmidt, Noah H. Hillman, Matthew W. Kemp, Alan H. Jobe

Research output: Contribution to journalArticle

Abstract

Background: The amount of surfactant deposited in the lungs and its overall pulmonary distribution determine the therapeutic outcome of surfactant replacement therapy. Most of the currently available methods to determine the intrapulmonary distribution of surfactant are time-consuming and require surfactant labelling. Our aim was to assess the potential of Mass Spectrometry Imaging (MSI) as a label-free technique to qualitatively and quantitatively evaluate the distribution of surfactant to the premature lamb. Methods: Twelve preterm lambs (gestational age 126-127d, term ~150d) were allocated in two experimental groups. Seven lambs were treated with an intratracheal bolus of the synthetic surfactant CHF5633 (200 mg/kg) and 5 lambs were managed with mechanical ventilation for 120 min, as controls. The right lung lobes of all lambs were gradually frozen while inflated to 20 cmH2O pressure for lung cryo-sections for MSI analysis. The intensity signals of SP-C analog and SP-B analog, the two synthetic peptides contained in the CHF5633 surfactant, were used to locate, map and quantify the intrapulmonary exogenous surfactant. Results: Surfactant treatment was associated with a significant improvement of the mean arterial oxygenation and lung compliance (p < 0.05). Nevertheless, the physiological response to surfactant treatment was not uniform across all animals. SP-C analog and SP-B analog were successfully imaged and quantified by means of MSI in the peripheral lungs of all surfactant-treated animals. The intensity of the signal was remarkably low in untreated lambs, corresponding to background noise. The signal intensity of SP-B analog in each surfactant-treated animal, which represents the surfactant distributed to the peripheral right lung, correlated well with the physiologic response as assessed by the area under the curves of the individual arterial partial oxygen pressure and dynamic lung compliance curves of the lambs. Conclusions: Applying MSI, we were able to detect, locate and quantify the amount of exogenous surfactant distributed to the lower right lung of surfactant-treated lambs. The distribution pattern of SP-B analog correlated well with the pulmonary physiological outcomes of the animals. MSI is a valuable label-free technique which is able to simultaneously evaluate qualitative and quantitative drug distribution in the lung.

Original languageEnglish
Article number175
JournalRespiratory Research
Volume20
Issue number1
DOIs
Publication statusPublished - 5 Aug 2019

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Surface-Active Agents
Mass Spectrometry
Lung
Lung Compliance
Partial Pressure
Therapeutics
Artificial Respiration
Gestational Age
Area Under Curve
Noise

Cite this

Zecchi, Riccardo ; Franceschi, Pietro ; Tigli, Laura ; Ricci, Francesca ; Boscaro, Francesca ; Pioselli, Barbara ; Mileo, Valentina ; Murgia, Xabier ; Bianco, Federico ; Salomone, Fabrizio ; Schmidt, Augusto F. ; Hillman, Noah H. ; Kemp, Matthew W. ; Jobe, Alan H. / Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs. In: Respiratory Research. 2019 ; Vol. 20, No. 1.
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abstract = "Background: The amount of surfactant deposited in the lungs and its overall pulmonary distribution determine the therapeutic outcome of surfactant replacement therapy. Most of the currently available methods to determine the intrapulmonary distribution of surfactant are time-consuming and require surfactant labelling. Our aim was to assess the potential of Mass Spectrometry Imaging (MSI) as a label-free technique to qualitatively and quantitatively evaluate the distribution of surfactant to the premature lamb. Methods: Twelve preterm lambs (gestational age 126-127d, term ~150d) were allocated in two experimental groups. Seven lambs were treated with an intratracheal bolus of the synthetic surfactant CHF5633 (200 mg/kg) and 5 lambs were managed with mechanical ventilation for 120 min, as controls. The right lung lobes of all lambs were gradually frozen while inflated to 20 cmH2O pressure for lung cryo-sections for MSI analysis. The intensity signals of SP-C analog and SP-B analog, the two synthetic peptides contained in the CHF5633 surfactant, were used to locate, map and quantify the intrapulmonary exogenous surfactant. Results: Surfactant treatment was associated with a significant improvement of the mean arterial oxygenation and lung compliance (p < 0.05). Nevertheless, the physiological response to surfactant treatment was not uniform across all animals. SP-C analog and SP-B analog were successfully imaged and quantified by means of MSI in the peripheral lungs of all surfactant-treated animals. The intensity of the signal was remarkably low in untreated lambs, corresponding to background noise. The signal intensity of SP-B analog in each surfactant-treated animal, which represents the surfactant distributed to the peripheral right lung, correlated well with the physiologic response as assessed by the area under the curves of the individual arterial partial oxygen pressure and dynamic lung compliance curves of the lambs. Conclusions: Applying MSI, we were able to detect, locate and quantify the amount of exogenous surfactant distributed to the lower right lung of surfactant-treated lambs. The distribution pattern of SP-B analog correlated well with the pulmonary physiological outcomes of the animals. MSI is a valuable label-free technique which is able to simultaneously evaluate qualitative and quantitative drug distribution in the lung.",
keywords = "CHF5633, Mass spectrometry imaging, Premature lambs, Respiratory distress syndrome, Surfactant",
author = "Riccardo Zecchi and Pietro Franceschi and Laura Tigli and Francesca Ricci and Francesca Boscaro and Barbara Pioselli and Valentina Mileo and Xabier Murgia and Federico Bianco and Fabrizio Salomone and Schmidt, {Augusto F.} and Hillman, {Noah H.} and Kemp, {Matthew W.} and Jobe, {Alan H.}",
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Zecchi, R, Franceschi, P, Tigli, L, Ricci, F, Boscaro, F, Pioselli, B, Mileo, V, Murgia, X, Bianco, F, Salomone, F, Schmidt, AF, Hillman, NH, Kemp, MW & Jobe, AH 2019, 'Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs' Respiratory Research, vol. 20, no. 1, 175. https://doi.org/10.1186/s12931-019-1144-5

Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs. / Zecchi, Riccardo; Franceschi, Pietro; Tigli, Laura; Ricci, Francesca; Boscaro, Francesca; Pioselli, Barbara; Mileo, Valentina; Murgia, Xabier; Bianco, Federico; Salomone, Fabrizio; Schmidt, Augusto F.; Hillman, Noah H.; Kemp, Matthew W.; Jobe, Alan H.

In: Respiratory Research, Vol. 20, No. 1, 175, 05.08.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mass spectrometry imaging as a tool for evaluating the pulmonary distribution of exogenous surfactant in premature lambs

AU - Zecchi, Riccardo

AU - Franceschi, Pietro

AU - Tigli, Laura

AU - Ricci, Francesca

AU - Boscaro, Francesca

AU - Pioselli, Barbara

AU - Mileo, Valentina

AU - Murgia, Xabier

AU - Bianco, Federico

AU - Salomone, Fabrizio

AU - Schmidt, Augusto F.

AU - Hillman, Noah H.

AU - Kemp, Matthew W.

AU - Jobe, Alan H.

PY - 2019/8/5

Y1 - 2019/8/5

N2 - Background: The amount of surfactant deposited in the lungs and its overall pulmonary distribution determine the therapeutic outcome of surfactant replacement therapy. Most of the currently available methods to determine the intrapulmonary distribution of surfactant are time-consuming and require surfactant labelling. Our aim was to assess the potential of Mass Spectrometry Imaging (MSI) as a label-free technique to qualitatively and quantitatively evaluate the distribution of surfactant to the premature lamb. Methods: Twelve preterm lambs (gestational age 126-127d, term ~150d) were allocated in two experimental groups. Seven lambs were treated with an intratracheal bolus of the synthetic surfactant CHF5633 (200 mg/kg) and 5 lambs were managed with mechanical ventilation for 120 min, as controls. The right lung lobes of all lambs were gradually frozen while inflated to 20 cmH2O pressure for lung cryo-sections for MSI analysis. The intensity signals of SP-C analog and SP-B analog, the two synthetic peptides contained in the CHF5633 surfactant, were used to locate, map and quantify the intrapulmonary exogenous surfactant. Results: Surfactant treatment was associated with a significant improvement of the mean arterial oxygenation and lung compliance (p < 0.05). Nevertheless, the physiological response to surfactant treatment was not uniform across all animals. SP-C analog and SP-B analog were successfully imaged and quantified by means of MSI in the peripheral lungs of all surfactant-treated animals. The intensity of the signal was remarkably low in untreated lambs, corresponding to background noise. The signal intensity of SP-B analog in each surfactant-treated animal, which represents the surfactant distributed to the peripheral right lung, correlated well with the physiologic response as assessed by the area under the curves of the individual arterial partial oxygen pressure and dynamic lung compliance curves of the lambs. Conclusions: Applying MSI, we were able to detect, locate and quantify the amount of exogenous surfactant distributed to the lower right lung of surfactant-treated lambs. The distribution pattern of SP-B analog correlated well with the pulmonary physiological outcomes of the animals. MSI is a valuable label-free technique which is able to simultaneously evaluate qualitative and quantitative drug distribution in the lung.

AB - Background: The amount of surfactant deposited in the lungs and its overall pulmonary distribution determine the therapeutic outcome of surfactant replacement therapy. Most of the currently available methods to determine the intrapulmonary distribution of surfactant are time-consuming and require surfactant labelling. Our aim was to assess the potential of Mass Spectrometry Imaging (MSI) as a label-free technique to qualitatively and quantitatively evaluate the distribution of surfactant to the premature lamb. Methods: Twelve preterm lambs (gestational age 126-127d, term ~150d) were allocated in two experimental groups. Seven lambs were treated with an intratracheal bolus of the synthetic surfactant CHF5633 (200 mg/kg) and 5 lambs were managed with mechanical ventilation for 120 min, as controls. The right lung lobes of all lambs were gradually frozen while inflated to 20 cmH2O pressure for lung cryo-sections for MSI analysis. The intensity signals of SP-C analog and SP-B analog, the two synthetic peptides contained in the CHF5633 surfactant, were used to locate, map and quantify the intrapulmonary exogenous surfactant. Results: Surfactant treatment was associated with a significant improvement of the mean arterial oxygenation and lung compliance (p < 0.05). Nevertheless, the physiological response to surfactant treatment was not uniform across all animals. SP-C analog and SP-B analog were successfully imaged and quantified by means of MSI in the peripheral lungs of all surfactant-treated animals. The intensity of the signal was remarkably low in untreated lambs, corresponding to background noise. The signal intensity of SP-B analog in each surfactant-treated animal, which represents the surfactant distributed to the peripheral right lung, correlated well with the physiologic response as assessed by the area under the curves of the individual arterial partial oxygen pressure and dynamic lung compliance curves of the lambs. Conclusions: Applying MSI, we were able to detect, locate and quantify the amount of exogenous surfactant distributed to the lower right lung of surfactant-treated lambs. The distribution pattern of SP-B analog correlated well with the pulmonary physiological outcomes of the animals. MSI is a valuable label-free technique which is able to simultaneously evaluate qualitative and quantitative drug distribution in the lung.

KW - CHF5633

KW - Mass spectrometry imaging

KW - Premature lambs

KW - Respiratory distress syndrome

KW - Surfactant

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U2 - 10.1186/s12931-019-1144-5

DO - 10.1186/s12931-019-1144-5

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JF - Respiratory Research

SN - 1465-9921

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