Skip to main content
Erschienen in: Magnetic Resonance Materials in Physics, Biology and Medicine 1/2019

12.11.2018 | Research Article

Preclinical 19F MRI cell tracking at 3 Tesla

verfasst von: Ashley V. Makela, Paula J. Foster

Erschienen in: Magnetic Resonance Materials in Physics, Biology and Medicine | Ausgabe 1/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To develop methods for fluorine-19 (19F) MRI cell tracking in mice on a 3 Tesla clinical scanner. Compared to iron-based cell tracking, 19F MRI has lower sensitivity and, consequently, preclinical 19F cell tracking has only been performed at relatively high magnetic field strengths (> 3 T). Here, we focus on using 19F MRI to detect macrophages in tumors; macrophage density is an indication of tumor aggressiveness and, therefore, 19F MRI could be used as an imaging biomarker.

Methods

Perfluorocarbon (PFC)-labeled macrophages were imaged at 3 T and NMR spectroscopy was performed to validate 19F spin quantification. In vivo 19F MRI was performed on tumor-bearing mice, post-PFC at both 9.4 T and 3 T. 3 T MRI utilized varying NEX and 19F images were analyzed two different ways for 19F quantification.

Results

As few as 25,000 cells could be detected as cell pellets at 3 T. 19F quantification in cell pellets by 3 T MRI agreed with NMR spectroscopy. 19F signal was observed in the liver, spleen and tumor in all mice at 9.4 T and 3 T and there was no significant difference in 19F spin quantification.

Conclusion

This study demonstrates the ability to detect and quantify 19F signal in murine tumors using 19F MRI at 3 T.
Literatur
1.
Zurück zum Zitat Balducci A, Helfer BM, Ahrens ET, O’Hanlon CF 3rd, Wesa AK (2012) Visualizing arthritic inflammation and therapeutic response by fluorine-19 magnetic resonance imaging (19F MRI). J Inflamm (Lond) 9:24CrossRef Balducci A, Helfer BM, Ahrens ET, O’Hanlon CF 3rd, Wesa AK (2012) Visualizing arthritic inflammation and therapeutic response by fluorine-19 magnetic resonance imaging (19F MRI). J Inflamm (Lond) 9:24CrossRef
2.
Zurück zum Zitat Shin SH, Kadayakkara DK, Bulte JWM (2017) In vivo (19)F MR imaging cell tracking of inflammatory macrophages and site-specific development of colitis-associated dysplasia. Radiology 282:194–201CrossRefPubMed Shin SH, Kadayakkara DK, Bulte JWM (2017) In vivo (19)F MR imaging cell tracking of inflammatory macrophages and site-specific development of colitis-associated dysplasia. Radiology 282:194–201CrossRefPubMed
3.
Zurück zum Zitat Zhong J, Narsinh K, Morel PA, Xu H, Ahrens ET (2015) In vivo quantification of inflammation in experimental autoimmune encephalomyelitis rats using fluorine-19 magnetic resonance imaging reveals immune cell recruitment outside the nervous system. PLoS One 10:e0140238CrossRefPubMedPubMedCentral Zhong J, Narsinh K, Morel PA, Xu H, Ahrens ET (2015) In vivo quantification of inflammation in experimental autoimmune encephalomyelitis rats using fluorine-19 magnetic resonance imaging reveals immune cell recruitment outside the nervous system. PLoS One 10:e0140238CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Makela AV, Gaudet JM, Foster PJ (2017) Quantifying tumor associated macrophages in breast cancer: a comparison of iron and fluorine-based MRI cell tracking. Sci Rep 7:42109CrossRefPubMedPubMedCentral Makela AV, Gaudet JM, Foster PJ (2017) Quantifying tumor associated macrophages in breast cancer: a comparison of iron and fluorine-based MRI cell tracking. Sci Rep 7:42109CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Makela AV, Foster PJ (2018) Imaging macrophage distribution and density in mammary tumors and lung metastases using fluorine-19 MRI cell tracking. Magn Reson Med 80:1138–1147CrossRefPubMed Makela AV, Foster PJ (2018) Imaging macrophage distribution and density in mammary tumors and lung metastases using fluorine-19 MRI cell tracking. Magn Reson Med 80:1138–1147CrossRefPubMed
6.
Zurück zum Zitat Khurana A, Chapelin F, Xu H, Acevedo JR, Molinolo A, Nguyen Q, Ahrens ET (2018) Visualization of macrophage recruitment in head and neck carcinoma model using fluorine-19 magnetic resonance imaging. Magn Reson Med 79:1972–1980CrossRefPubMed Khurana A, Chapelin F, Xu H, Acevedo JR, Molinolo A, Nguyen Q, Ahrens ET (2018) Visualization of macrophage recruitment in head and neck carcinoma model using fluorine-19 magnetic resonance imaging. Magn Reson Med 79:1972–1980CrossRefPubMed
7.
Zurück zum Zitat Shin SH, Park SH, Kang SH, Kim SW, Kim M, Kim D (2017) Fluorine-19 magnetic resonance imaging and positron emission tomography of tumor-associated macrophages and tumor metabolism. Contrast Media Mol Imaging 2017:4896310CrossRefPubMedPubMedCentral Shin SH, Park SH, Kang SH, Kim SW, Kim M, Kim D (2017) Fluorine-19 magnetic resonance imaging and positron emission tomography of tumor-associated macrophages and tumor metabolism. Contrast Media Mol Imaging 2017:4896310CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Srinivas M, Boehm-Sturm P, Figdor CG, de Vries IJ, Hoehn M (2012) Labeling cells for in vivo tracking using (19)F MRI. Biomaterials 33:8830–8840CrossRefPubMed Srinivas M, Boehm-Sturm P, Figdor CG, de Vries IJ, Hoehn M (2012) Labeling cells for in vivo tracking using (19)F MRI. Biomaterials 33:8830–8840CrossRefPubMed
9.
Zurück zum Zitat Taylor AJ, Granwehr J, Lesbats C, Krupa JL, Six JS, Pavlovskaya GE, Thomas NR, Auer DP, Meersmann T, Faas HM (2016) Probe-specific procedure to estimate sensitivity and detection limits for 19F magnetic resonance imaging. PLoS One 11:e0163704CrossRefPubMedPubMedCentral Taylor AJ, Granwehr J, Lesbats C, Krupa JL, Six JS, Pavlovskaya GE, Thomas NR, Auer DP, Meersmann T, Faas HM (2016) Probe-specific procedure to estimate sensitivity and detection limits for 19F magnetic resonance imaging. PLoS One 11:e0163704CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Temme S, Grapentin C, Quast C, Jacoby C, Grandoch M, Ding Z, Owenier C, Mayenfels F, Fischer JW, Schubert R, Schrader J, Flogel U (2015) Noninvasive imaging of early venous thrombosis by 19F magnetic resonance imaging with targeted perfluorocarbon nanoemulsions. Circulation 131:1405–1414CrossRefPubMed Temme S, Grapentin C, Quast C, Jacoby C, Grandoch M, Ding Z, Owenier C, Mayenfels F, Fischer JW, Schubert R, Schrader J, Flogel U (2015) Noninvasive imaging of early venous thrombosis by 19F magnetic resonance imaging with targeted perfluorocarbon nanoemulsions. Circulation 131:1405–1414CrossRefPubMed
11.
Zurück zum Zitat Ebner B, Behm P, Jacoby C, Burghoff S, French BA, Schrader J, Flogel U (2010) Early assessment of pulmonary inflammation by 19F MRI in vivo. Circ Cardiovasc Imaging 3:202–210CrossRefPubMedPubMedCentral Ebner B, Behm P, Jacoby C, Burghoff S, French BA, Schrader J, Flogel U (2010) Early assessment of pulmonary inflammation by 19F MRI in vivo. Circ Cardiovasc Imaging 3:202–210CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Hitchens TK, Ye Q, Eytan DF, Janjic JM, Ahrens ET, Ho C (2011) 19F MRI detection of acute allograft rejection with in vivo perfluorocarbon labeling of immune cells. Magn Reson Med 65:1144–1153CrossRefPubMedPubMedCentral Hitchens TK, Ye Q, Eytan DF, Janjic JM, Ahrens ET, Ho C (2011) 19F MRI detection of acute allograft rejection with in vivo perfluorocarbon labeling of immune cells. Magn Reson Med 65:1144–1153CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Flögel U, Su S, Kreideweiß I, Ding Z, Galbarz L, Fu J, Jacoby C, Witzke O, Schrader J (2011) Noninvasive detection of graft rejection by in vivo 19F MRI in the early stage. Am J Transplant 11:235–244CrossRefPubMed Flögel U, Su S, Kreideweiß I, Ding Z, Galbarz L, Fu J, Jacoby C, Witzke O, Schrader J (2011) Noninvasive detection of graft rejection by in vivo 19F MRI in the early stage. Am J Transplant 11:235–244CrossRefPubMed
14.
Zurück zum Zitat Srinivas M, Morel PA, Ernst LA, Laidlaw DH, Ahrens ET (2007) Fluorine-19 MRI for visualization and quantification of cell migration in a diabetes model. Magn Reson Med 58:725–734CrossRefPubMed Srinivas M, Morel PA, Ernst LA, Laidlaw DH, Ahrens ET (2007) Fluorine-19 MRI for visualization and quantification of cell migration in a diabetes model. Magn Reson Med 58:725–734CrossRefPubMed
15.
16.
Zurück zum Zitat Tiainen S, Tumelius R, Rilla K, Hämäläinen K, Tammi M, Tammi R, Kosma VM, Oikari S, Auvinen P (2015) High numbers of macrophages, especially M2-like (CD163-positive), correlate with hyaluronan accumulation and poor outcome in breast cancer. Histopathology 66:873–883CrossRefPubMed Tiainen S, Tumelius R, Rilla K, Hämäläinen K, Tammi M, Tammi R, Kosma VM, Oikari S, Auvinen P (2015) High numbers of macrophages, especially M2-like (CD163-positive), correlate with hyaluronan accumulation and poor outcome in breast cancer. Histopathology 66:873–883CrossRefPubMed
17.
Zurück zum Zitat Yuan Z-Y, Luo R-Z, Peng R-J, Wang S-S, Xue C (2014) High infiltration of tumor-associated macrophages in triple-negative breast cancer is associated with a higher risk of distant metastasis. Onco Targets Ther 7:1475–1480CrossRefPubMedPubMedCentral Yuan Z-Y, Luo R-Z, Peng R-J, Wang S-S, Xue C (2014) High infiltration of tumor-associated macrophages in triple-negative breast cancer is associated with a higher risk of distant metastasis. Onco Targets Ther 7:1475–1480CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Gwak JM, Jang MH, Il Kim D, Seo AN, Park SY (2015) Prognostic value of tumor-associated macrophages according to histologic locations and hormone receptor status in breast cancer. PLoS One 10:1–14CrossRef Gwak JM, Jang MH, Il Kim D, Seo AN, Park SY (2015) Prognostic value of tumor-associated macrophages according to histologic locations and hormone receptor status in breast cancer. PLoS One 10:1–14CrossRef
19.
Zurück zum Zitat Reigstad I, Smeland HYH, Skogstrand T, Sortland K, Schmid MC, Reed RK, Stuhr L (2016) Stromal integrin α11β1 affects RM11 prostate and 4T1 breast xenograft tumors differently. PLoS One 11:e0151663CrossRefPubMedPubMedCentral Reigstad I, Smeland HYH, Skogstrand T, Sortland K, Schmid MC, Reed RK, Stuhr L (2016) Stromal integrin α11β1 affects RM11 prostate and 4T1 breast xenograft tumors differently. PLoS One 11:e0151663CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Wong CW, Song C, Grimes MM, Fu W, Dewhirst MW, Muschel RJ, Al-Mehdi A-B (2002) Intravascular location of breast cancer cells after spontaneous metastasis to the lung. Am J Pathol 161:749–753CrossRefPubMedPubMedCentral Wong CW, Song C, Grimes MM, Fu W, Dewhirst MW, Muschel RJ, Al-Mehdi A-B (2002) Intravascular location of breast cancer cells after spontaneous metastasis to the lung. Am J Pathol 161:749–753CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Wu YL, Ye Q, Foley LM, Hitchens TK, Sato K, Williams JB, Ho C (2006) In situ labeling of immune cells with iron oxide particles: an approach to detect organ rejection by cellular MRI. Proc Natl Acad Sci USA 103:1852–1857CrossRefPubMed Wu YL, Ye Q, Foley LM, Hitchens TK, Sato K, Williams JB, Ho C (2006) In situ labeling of immune cells with iron oxide particles: an approach to detect organ rejection by cellular MRI. Proc Natl Acad Sci USA 103:1852–1857CrossRefPubMed
23.
Zurück zum Zitat Zarif L, Postel M, Trevino L, Riess JG, Valla A, Follana R (1994) Biodistribution and excretion of a mixed fluorocarbon-hydrocarbon “dowel” emulsion as determined by 19F NMR. Artif Cells Blood Substit Immobil Biotechnol 22:1193–1198CrossRefPubMed Zarif L, Postel M, Trevino L, Riess JG, Valla A, Follana R (1994) Biodistribution and excretion of a mixed fluorocarbon-hydrocarbon “dowel” emulsion as determined by 19F NMR. Artif Cells Blood Substit Immobil Biotechnol 22:1193–1198CrossRefPubMed
25.
Zurück zum Zitat Wang Y-XJ (2011) Superparamagnetic iron oxide based MRI contrast agents: current status of clinical application. Quant Imaging Med Surg 1:35–40PubMedPubMedCentral Wang Y-XJ (2011) Superparamagnetic iron oxide based MRI contrast agents: current status of clinical application. Quant Imaging Med Surg 1:35–40PubMedPubMedCentral
27.
Zurück zum Zitat Khurana A, Chapelin F, Xu H, Acevedo JR, Molinolo A, Nguyen Q, Ahrens ET (2017) Visualization of macrophage recruitment in head and neck carcinoma model using fluorine-19 magnetic resonance imaging. Magn Reson Med 79:1972–1980CrossRefPubMedPubMedCentral Khurana A, Chapelin F, Xu H, Acevedo JR, Molinolo A, Nguyen Q, Ahrens ET (2017) Visualization of macrophage recruitment in head and neck carcinoma model using fluorine-19 magnetic resonance imaging. Magn Reson Med 79:1972–1980CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Weibel S, Basse-Luesebrink TC, Hess M, Hofmann E, Seubert C, Langbein-Laugwitz J, Gentschev I, Sturm VJF, Ye Y, Kampf T, Jakob PM, Szalay AA (2013) Imaging of intratumoral inflammation during oncolytic virotherapy of tumors by 19F-magnetic resonance imaging (MRI). PLoS One 8:e56317CrossRefPubMedPubMedCentral Weibel S, Basse-Luesebrink TC, Hess M, Hofmann E, Seubert C, Langbein-Laugwitz J, Gentschev I, Sturm VJF, Ye Y, Kampf T, Jakob PM, Szalay AA (2013) Imaging of intratumoral inflammation during oncolytic virotherapy of tumors by 19F-magnetic resonance imaging (MRI). PLoS One 8:e56317CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Balducci A, Wen Y, Zhang Y, Helfer BM, Hitchens TK, Meng WS, Wesa AK, Janjic JM (2013) A novel probe for the non-invasive detection of tumor-associated inflammation. Oncoimmunology 2:e23034CrossRefPubMedPubMedCentral Balducci A, Wen Y, Zhang Y, Helfer BM, Hitchens TK, Meng WS, Wesa AK, Janjic JM (2013) A novel probe for the non-invasive detection of tumor-associated inflammation. Oncoimmunology 2:e23034CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Daldrup-Link HE, Golovko D, Ruffell B, Denardo DG, Castaneda R, Ansari C, Rao J, Tikhomirov GA, Wendland MF, Corot C, Coussens LM (2011) MRI of tumor-associated macrophages with clinically applicable iron oxide nanoparticles. Clin Cancer Res 17:5695–5704CrossRefPubMedPubMedCentral Daldrup-Link HE, Golovko D, Ruffell B, Denardo DG, Castaneda R, Ansari C, Rao J, Tikhomirov GA, Wendland MF, Corot C, Coussens LM (2011) MRI of tumor-associated macrophages with clinically applicable iron oxide nanoparticles. Clin Cancer Res 17:5695–5704CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Shi Q, Pisani LJ, Lee YK, Messing S, Ansari C, Bhaumik S, Lowery L, Lee BD, Meyer DE, Daldrup-Link HE (2013) Evaluation of the novel USPIO GEH121333 for MR imaging of cancer immune responses. Contrast Media Mol Imaging 8:281–288CrossRefPubMedPubMedCentral Shi Q, Pisani LJ, Lee YK, Messing S, Ansari C, Bhaumik S, Lowery L, Lee BD, Meyer DE, Daldrup-Link HE (2013) Evaluation of the novel USPIO GEH121333 for MR imaging of cancer immune responses. Contrast Media Mol Imaging 8:281–288CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Leimgruber A, Berger C, Cortez-Retamozo V, Etzrodt M, Newton AP, Waterman P, Figueiredo JL, Kohler RH, Elpek N, Mempel TR, Swirski FK, Nahrendorf M, Weissleder R, Pittet MJ (2009) Behavior of endogenous tumor-associated macrophages assessed in vivo using a functionalized nanoparticle. Neoplasia 11:459-IN4CrossRef Leimgruber A, Berger C, Cortez-Retamozo V, Etzrodt M, Newton AP, Waterman P, Figueiredo JL, Kohler RH, Elpek N, Mempel TR, Swirski FK, Nahrendorf M, Weissleder R, Pittet MJ (2009) Behavior of endogenous tumor-associated macrophages assessed in vivo using a functionalized nanoparticle. Neoplasia 11:459-IN4CrossRef
33.
Zurück zum Zitat Ahrens ET, Young W-B, Xu H, Pusateri LK (2011) Rapid quantification of inflammation in tissue samples using perfluorocarbon emulsion and fluorine-19 nuclear magnetic resonance. Biotechniques 50:229–234CrossRefPubMedPubMedCentral Ahrens ET, Young W-B, Xu H, Pusateri LK (2011) Rapid quantification of inflammation in tissue samples using perfluorocarbon emulsion and fluorine-19 nuclear magnetic resonance. Biotechniques 50:229–234CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Ahrens ET, Helfer BM, O’Hanlon CF, Schirda C (2014) Clinical cell therapy imaging using a perfluorocarbon tracer and fluorine-19 MRI. Magn Reson Med 72:1696–1701CrossRefPubMedPubMedCentral Ahrens ET, Helfer BM, O’Hanlon CF, Schirda C (2014) Clinical cell therapy imaging using a perfluorocarbon tracer and fluorine-19 MRI. Magn Reson Med 72:1696–1701CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Gocheva V, Wang H-W, Gadea BB, Shree T, Hunter KE, Garfall AL, Berman T, Joyce JA (2010) IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev 24:241–255CrossRefPubMedPubMedCentral Gocheva V, Wang H-W, Gadea BB, Shree T, Hunter KE, Garfall AL, Berman T, Joyce JA (2010) IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev 24:241–255CrossRefPubMedPubMedCentral
36.
Zurück zum Zitat Wyckoff JB, Wang Y, Lin EY, Li JF, Goswami S, Stanley ER, Segall JE, Pollard JW, Condeelis J (2007) Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res 67:2649–2656CrossRefPubMed Wyckoff JB, Wang Y, Lin EY, Li JF, Goswami S, Stanley ER, Segall JE, Pollard JW, Condeelis J (2007) Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res 67:2649–2656CrossRefPubMed
37.
Zurück zum Zitat Hill HDW, Richards RE (1968) Limits of measurement in magnetic resonance. J Phys E 1:977CrossRef Hill HDW, Richards RE (1968) Limits of measurement in magnetic resonance. J Phys E 1:977CrossRef
38.
Zurück zum Zitat Haase A, Odoj F, Von Kienlin M, Warnking J, Fidler F, Weisser A, Nittka M, Rommel E, Lanz T, Kalusche B, Griswold M (2000) NMR probeheads for in vivo applications. Concepts Magn Reson 12:361–388CrossRef Haase A, Odoj F, Von Kienlin M, Warnking J, Fidler F, Weisser A, Nittka M, Rommel E, Lanz T, Kalusche B, Griswold M (2000) NMR probeheads for in vivo applications. Concepts Magn Reson 12:361–388CrossRef
39.
Zurück zum Zitat Morita Y, Zhang R, Leslie M, Adhikari S, Hasan N, Chervoneva I, Rui H, Tanaka T (2017) Pathologic evaluation of tumor-associated macrophage density and vessel inflammation in invasive breast carcinomas. Oncol Lett 14:2111–2118CrossRefPubMedPubMedCentral Morita Y, Zhang R, Leslie M, Adhikari S, Hasan N, Chervoneva I, Rui H, Tanaka T (2017) Pathologic evaluation of tumor-associated macrophage density and vessel inflammation in invasive breast carcinomas. Oncol Lett 14:2111–2118CrossRefPubMedPubMedCentral
Metadaten
Titel
Preclinical 19F MRI cell tracking at 3 Tesla
verfasst von
Ashley V. Makela
Paula J. Foster
Publikationsdatum
12.11.2018
Verlag
Springer International Publishing
Erschienen in
Magnetic Resonance Materials in Physics, Biology and Medicine / Ausgabe 1/2019
Print ISSN: 0968-5243
Elektronische ISSN: 1352-8661
DOI
https://doi.org/10.1007/s10334-018-0715-7

Weitere Artikel der Ausgabe 1/2019

Magnetic Resonance Materials in Physics, Biology and Medicine 1/2019 Zur Ausgabe

Update Radiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.