https://openworks.mdanderson.org/sumexp21/1226/thumbnail.jp

Cressman, Erik

Crouch, A. Colleen

Stolley, Danielle

Warar, Shubhneet

English

OpenWorks @ MD Anderson

IntroductionThe incidence and mortality of liver cancer are bothincreasing and there is no curative medical treatment [1].Embolization is a promising treatment option in which anembolic agent, ethiodized oil (iodinated ethyl esters frompoppy seed oil), is often utilized in combination withdrugs to disrupt tumor arterial supply [2]. The oil is anideal radiopaque contrast agent for imaging usingcomputed tomography (CT) due to the presence ofiodine [3]; however, characterization of ethiodized oilwith mass spectrometry imagining (MSI) was unknown.Herein, we characterize the mixture of compoundscomprising ethiodized oil using matrix-assisted laserdesorption ionization (MALDI)-MSI.MethodsMALDI Matrices: Three matrices were tested onethiodized oil (Guerbet LLC) by spotting a 1:1 ratio ofsolution to matrix on a standard MALDI well plate asfollows: for positive ion mode, 2,5-dihydroxybenzoic acid(DHB) and alpha-cyano-4-hydroxycinnamic acid(CHCA); for negative ion mode, 9-aminoacridinehydrochloride (9AA).Tissue Preparation: Ethiodized oil was spotted onsectioned tissue and matrix was applied uniformlyacross by a HTX M5 robotic sprayer.Analysis: MALDI time-of-flight (TOF) mass spectrometrywas performed on a Waters Synapt G2-Si. MS/MS wasdone with optimized transfer collision energies forselected peaks to further characterize features. Dataprocessing and images were reconstructed usingHDImaging software.ResultsConclusionsEthiodized oil is a common clinical contrast agent, butexact structures of the mixture are not reported. Todetermine chemical composition, MS peaks can beanalyzed and compared to endogenous peaks in tissue.The mass spectra were consistent with the oil being amixture of compounds with iodinated long-chain fattyacid esters. Compounds were determined to havebetween 1-3 iodines per structure. By characterizing MSpeaks, researchers can now track distribution ofethiodized oil in tissues. By detecting the oil in tissue,other drugs dissolved in the oil could be more easilytraced.References[1] Cressman, E. N.; Guo, C. CardioVascular and Interventional Radiology 2018, 41 (10), 1611–1617. [2] Uchida, H.; Ohishi, H.; Matsuo, N.; Nishimine, K.; Ohue, S.; Nishimura, Y.; Maeda, M.; Yoshioka, T. Cardiovascular and Interventional Radiology 1990, 13 (3), 140–145. [3] Lipiodol (Ethiodized Oil) Injection; Guerbet US: Princeton, NJ, USA, 2018.Acknowledgements Thank you to MD Anderson Cancer Center and theBaylor University Honors College for sponsoring theUniversity Outreach Summer Program’s UndergraduateCancer Research Internship. This work was alsosupported by a training fellowship from The University ofTexas Health Science Center at Houston Center forClinical and Translational Sciences TL1 Program (NIHGrant TL1 TR003169).Scheme 1:Typical MSI workflow. Cryosectioned tissue is frozen-mounted on a regularglass slide. After drying under vacuum for 10 minutes, MALDI matrix isapplied using a robotic sprayer. Data was acquired from m/z 50-1200 andprocessed using HDImaging software.Mass Spectrometry Imaging Characterization of Ethiodized Oil,  a Radiopaque Hydrophobic Multipurpose Liquid Used in Cancer Therapy    Shubhneet Warar1, Danielle Stolley2, A. Colleen Crouch2, Erik Cressman21: Baylor University, Waco, TX;   2: University of Texas MD Anderson Cancer Center, Houston, TXMass Spectrometry Imaging WorkflowFigure 3:HDImaging software image reconstruction of ethiodized oil spotted onsectioned tissue in negative mode at m/z 292.7711 (top image) and m/z370.1321 (bottom image). Left tissues show ethiodized oil spotted in themiddle. Right tissues show a mixture of ethiodized oil, dichloroacetic acid,caffeine, and benzethonium chloride spotted in the middle. Intensity ofcompounds is depicted by the shown color scale. Yellow circular spot onthe left tissue in the top image likely shows ethiodized oil. The bottomimage shows that matrix was possibly not adhering to the ethiodized oil, aslippery and difficult to dry substance, and thus not ionizing.m/z50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 1150 1200 1250 1300 1350 1400 1450 1500 1550 1600 1650 1700 1750 1800 1850 1900 1950%0100m/z50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 1150 1200 1250 1300 1350 1400 1450 1500 1550 1600 1650 1700 1750 1800 1850 1900 1950%0100m/z50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 1150 1200 1250 1300 1350 1400 1450 1500 1550 1600 1650 1700 1750 1800 1850 1900 1950%0100m/z50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 1150 1200 1250 1300 1350 1400 1450 1500 1550 1600 1650 1700 1750 1800 1850 1900 1950%0100m/z50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 1150 1200 1250 1300 1350 1400 1450 1500 1550 1600 1650 1700 1750 1800 1850 1900 1950%010020210707_C3_LIPIODOL_9AA_MSMS_508 23 (0.410) AM2 (Ar,20000.0,0.00,0.00); Cm (7:24) TOF MSMS 508.60LD- 1.56e3508.5759316.7396210.8377126.9043125.5541 160.8447!210.0141302.0047!236.8248318.7404506.5794381.7103328.7468!492.5866389.6753 !422.6715520.5859!521.17441003.58311002.6725!522.6265593.3290 953.9450871.7658621.8903 650.6890!847.9572682.66721007.61451261.69081237.18741082.76561101.6427 1538.65691275.4463 1446.4845 1825.194120210707_C3_LIPIODOL_9AA_MSMS_436 34 (0.596) AM2 (Ar,20000.0,0.00,0.00); Cm (7:38) TOF MSMS 436.70LD- 1.43e5126.9048118.897578.9590436.6496434.6541328.7413236.8061!144.8706 193.0779 248.7869 433.6584385.1257444.64151325.3853760.0472481.0447 607.3481 772.5314 1145.0637817.0203 1212.1465 1338.0713!1694.5797!1543.66661523.06791410.4709 1575.5847!1660.5126 !1806.34921777.7795!1833.472020210707_C3_LIPIODOL_9AA_MSMS_344 10 (0.185) AM2 (Ar,20000.0,0.00,0.00); Cm (7:25) TOF MSMS 344.70LD- 2.56e4126.9045118.902578.9628344.7140342.7184236.8049144.8699 230.8246 246.8206329.7498346.7105355.09961263.1234710.2689672.8547464.0895 621.8297 983.1793801.4771!742.7471 818.9878 1225.9167 1372.5690!1905.622620210707_C3_LIPIODOL_9AA 10 (0.187) AM2 (Ar,20000.0,0.00,0.00); Cm (7:20) TOF MS LD- 2.21e5273.0333193.0771191.0615126.9041112.9839 189.0471265.1465!194.0612!194.0818385.1445!274.0267344.7133315.0314275.0290436.6482386.1450432.6540497.1652444.6424 !627.2029530.5787!555.1505 672.1791 770.8980725.1578 958.2018810.2648!866.2599 910.2032 1092.88941004.1714 1047.1567 1419.34071188.2810!1149.2366 1724.6365!1877.466120210706_C1_MATRIX_9AA 9 (0.171) AM2 (Ar,20000.0,0.00,0.00); Cm (7:18) TOF MS LD- 2.65e5193.0766191.0609189.0448160.840978.9573385.1441273.0331272.7664!194.0785265.1465!239.0377318.9490320.9462370.1330386.1437414.6866 526.5565!440.6481 !558.5457!590.5425!628.5223!652.5187 !708.4972!747.4312 764.4399m/z9AA MatrixEthiodized Oil & 9AA MatrixMS/MS at m/z 344.7NegativeModem/z50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 1150 1200 1250 1300 1350 1400 1450 1500 1550 1600 1650 1700 1750 1800 1850 1900 1950%0100m/z50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 1150 1200 1250 1300 1350 1400 1450 1500 1550 1600 1650 1700 1750 1800 1850 1900 1950%0100m/z50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 1150 1200 1250 1300 1350 1400 1450 1500 1550 1600 1650 1700 1750 1800 1850 1900 1950%0100m/z50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 1150 1200 1250 1300 1350 1400 1450 1500 1550 1600 1650 1700 1750 1800 1850 1900 1950%0100m/z50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 1150 1200 1250 1300 1350 1400 1450 1500 1550 1600 1650 1700 1750 1800 1850 1900 1950%0100m/z50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 1150 1200 1250 1300 1350 1400 1450 1500 1550 1600 1650 1700 1750 1800 1850 1900 1950%010020210707_E3_LIPIODOL_DHB_MSMS_412_2 12 (0.221) AM2 (Ar,20000.0,0.00,0.00); Cm (7:15) TOF MSMS 412.30LD+ 1.25e591.054472.0808320.258192.0579208.1339!135.0813 149.0960233.1894300.1952321.2614412.3164322.2623!520.0977425.2572 504.0990 742.8259685.9528574.4002!664.9088609.1071 1348.69311121.6581!892.1346775.3110!830.2437 942.3488 1050.0261!982.1024 1134.3740 1674.41691400.2869 1566.1212!1592.4681 1888.56641819.15521688.1659 1964.9104 1980.102720210707_E3_LIPIODOL_DHB_MSMS_412 15 (0.272) AM2 (Ar,20000.0,0.00,0.00); Cm (7:18) TOF MSMS 412.30LD+ 3.17e6412.3213320.258672.0809 300.195691.0546 116.1074 277.2180233.1902147.0825 321.2617 410.3029413.3239414.32751087.1897502.1757441.7701 695.3577586.3862547.4796 683.3957609.9380 759.6346 784.4596 1506.95481382.93081311.32351187.9249!1126.7059!1209.9896 1257.7263 !1454.15601396.7688!1540.3049 1831.54691624.0216 1644.8057!1690.8401 1917.24051871.3857 1934.434420210707_E3_LIPIODOL_DHB_MSMS_320_2 20 (0.358) AM2 (Ar,20000.0,0.00,0.00); Cm (7:26) TOF MSMS 320.30LD+ 5.36e472.0806118.078291.0543135.0812 260.0689232.0743204.1383 274.0869 317.0672 !392.9293 1126.0240!704.1164!527.3958509.5101 543.0707 688.2056!911.6374!1086.98681035.25011008.4374!1154.5385 1384.3893!1351.6372 1400.3015 1635.37261609.3879 1677.0563 1918.415920210707_E3_LIPIODOL_DHB_MSMS_320 9 (0.169) AM2 (Ar,20000.0,0.00,0.00); Cm (7:22) TOF MSMS 320.30LD+ 5.44e4320.258472.0810208.133173.0856 106.9949 161.0425233.1888 318.0774322.2737332.0922333.1843 !708.2363590.9601!520.0246462.5402375.4241 559.7571 681.1659605.0028 894.6317720.1842 1118.0828911.6195 1134.3939 1371.3127 1501.56481400.7209!1616.74541522.7377!1966.54261885.965520210707_E3_LIPIODOL_DHB 10 (0.188) AM2 (Ar,20000.0,0.00,0.00); Cm (7:31) TOF MS LD+ 5.48e6412.3228273.0396137.0243103.076689.0600257.2473195.0923 320.2584331.1715374.1922413.3250467.1104414.3275 652.4728624.4695493.1262 591.4434519.3484 751.3829654.4785 723.3530 875.7156773.4023 851.3162 903.7432 1031.6604962.2164977.6616 1057.670520210706_E1_MATRIX_DHB 12 (0.224) AM2 (Ar,20000.0,0.00,0.00); Cm (7:12) TOF MS LD+ 2.58e6357.9770313.9863312.9786273.0391137.0236109.028880.9478269.9971229.0491195.0910 310.9644360.3620361.9713380.9633510.9951450.0022 868.9714558.9040 715.9517644.8492576.9149 662.8587 736.9270 773.8688 1071.9146922.8894!1016.81921003.8025!1121.8342!1173.7866m/z50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 1150 1200 1250 1300 1350 1400 1450 1500 1550 1600 1650 1700 1750 1800 1850 1900 1950%0100m/z50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 1150 1200 1250 1300 1350 1400 1450 1500 1550 1600 1650 1700 1750 1800 1850 1900 1950%0100m/z50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 1150 1200 1250 1300 1350 1400 1450 1500 1550 1600 1650 1700 1750 1800 1850 1900 1950%0100m/z50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 1150 1200 1250 1300 1350 1400 1450 1500 1550 1600 1650 1700 1750 1800 1850 1900 1950%0100m/z50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 1150 1200 1250 1300 1350 1400 1450 1500 1550 1600 1650 1700 1750 1800 1850 1900 1950%0100m/z50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 1150 1200 1250 1300 1350 1400 1450 1500 1550 1600 1650 1700 1750 1800 1850 1900 1950%0I I 412_2 12 (0.221) AM2 (Ar,20 00.0,0.00,0.00); Cm (7:15) TOF MSMS 412.30LD+ 1.25e591.054472.0808320.258192.0579208.1339!135.0813 149.0960233.1894300.1952321.2614412.3164322.2623!520.0977425.2572 504.0990 742.8259685.9528574.4002!664.9088609.1071 1348.69311121.6581!892.1346775.3110!830.2437 942.3488 1050.0261!982.1024 1134.3740 1674.41691400.2869 1566.1212!1592.4681 1888.56641819.15521688.1659 1964.9104 1980.102720210707_ 3_LI I L_ _MSMS_412 15 (0.272) AM2 (Ar,20000.0,0.00,0.00); Cm (7:18) TOF MSMS 412.30LD+ 3.17e6412.3213320.258672.0809 300.195691.0546 116.1074 277.2180233.1902147.0825 321.2617 410.3029413.3239414.32751087.1897502.1757441.7701 695.3577586.3862547.4796 683.3957609.9380 759.6346 784.4596 1506.95481382.93081311.32351187.9249!1126.7059!1209.9896 1257.7263 !1454.15601396.7688!1540.3049 1831.54691624.0216 1644.8057!1690.8401 1917.24051871.3857 1934.434420210707_E3_LIPIODOL_DHB_MSMS_320_2 20 (0.358) AM2 (Ar,20000.0,0.00,0.00); Cm (7:26) TOF MSMS 320.30LD+ 5.36e472.0806118.078291.0543135.0812 260.0689232.0743204.1383 274.0869 317.0672 !392.9293 1126.0240!704.1164!527.3958509.5101 543.0707 688.2056!911.6374!1086.98681035.25011008.4374!1154.5385 1384.3893!1351.6372 1400.3015 1635.37261609.3879 1677.0563 1918.415920210707_E3_LIPIODOL_DHB_MSMS_320 9 (0.169) AM2 (Ar,20000.0,0.00,0.00); Cm (7:22) TOF MSMS 320.30LD+ 5.44e4320.258472.0810208.133173.0856 106.9949 161.0425233.1888 318.0774322.2737332.0922333.1843 !708.2363590.9601!520.0246462.5402375.4241 559.7571 681.1659605.0028 894.6317720.1842 1118.0828911.6195 1134.3939 1371.3127 1501.56481400.7209!1616.74541522.7377!1966.54261885.965520210707_E3_LIPIODOL_DHB 10 (0.188) AM2 (Ar,20000.0,0.00,0.00); Cm (7:31) TOF MS LD+ 5.48e6412.3228273.0396137.0243103.076689.0600257.2473195.0923 320.2584331.1715374.1922413.3250467.1104414.3275 652.4728624.4695493.1262 591.4434519.3484 751.3829654.4785 723.3530 875.7156773.4023 851.3162 903.7432 1031.6604962.2164977.6616 1057.670520210706_E1_MATRIX_DHB 12 (0.224) AM2 (Ar,20000.0,0.00,0.00); Cm (7:12) TOF MS LD+ 2.58e6357.9770313.9863312.9786273.0391137.0236109.028880.9478269.9971229.0491195.0910 310.9644360.3620361.9713380.9633510.9951450.0022 868.9714558.9040 715.9517644.8492576.9149 662.8587 736.9270 773.8688 1071.9146922.8894!1016.81921003.8025!1121.8342!1173.7866m/zDHB MatrixEthiodized Oil & DHB MatrixMS/MS at m/z 412.3Positive ModeFigure 1:Mass spectra of ethiodized oil and 9AA matrix spotted on standard MALDIplate in negative mode. Spectra labels are as follows: bottom spectrumshows only matrix, middle spectrum shows matrix and ethiodized oil, topspectrum shows MS/MS fragments at m/z 344.7. Distinct peaks were seenat m/z 344.71, 436.68, and 508.58. For both precursor ions m/z 344.71 and436.68, only a fragment peak at 126.90 was seen and assigned to iodide asethiodized oil is an iodinated mixture. For the precursor ion m/z 508.58,fragment peaks were seen at 126.90, 169.46, 210.83, and 316.74. Oilspotted on tissue again showed an iodine peak at m/z 126.90.Figure 2:Mass spectra of ethiodized oil and DHB matrix spotted on standard MALDIplate in positive mode. Spectra labels are as follows: bottom spectrumshows only matrix, middle spectrum shows matrix and ethiodized oil, topspectrum shows MS/MS fragments at m/z 412.3. Using either DHB orCHCA, distinct MS peaks were seen at m/z 320.25 and 412.32. For theprecursor feature at m/z 320.25, MS/MS analysis showed fragment peaksat 72.08 and 208.13. For the precursor ion m/z 412.32, fragment peakswere seen at 72.08, 91.05, 208.13, and 320.26. Mass spectra of spottedtissue in both positive and negative mode showed similar precursor peaksbut with weaker intensity as endogenous lipids were of higher intensity.

Mass Spectrometry Imaging Characterization of Ethiodized Oil, a Radiopaque Hydrophobic Multipurpose Liquid Used in Cancer Therapy

https://openworks.mdanderson.org/cgi/viewcontent.cgi?article=1226&context=sumexp21

Mass Spectrometry Imaging Characterization of Ethiodized Oil, a Radiopaque Hydrophobic Multipurpose Liquid Used in Cancer Therapy

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