Novel Reporter Agents

novel reporter agents

A vast array of potential reporter molecules exists based on many diverse imaging modalities: we have investigated methods of assessing pO2 and/or hypoxia, pH and specific enzyme activity (β-galactosidase).

Many of the agents exploit a 19F signal and we have prepared several reviews on the development of the field. Judicious choice of molecule can often provide proton MRI analogs, though sophisticated water suppression may be required for effective imaging.

Most recently, we have enjoyed a productive collaboration with Professor Lippert at SMU, who has developed several new imaging reporter molecules based on chemiluminescence.


"19F NMR: clinical and molecular imaging applications" V. D. Kodibagkar, R. Hallac, D. Zhao, J.X. Yu, and R.P. Mason in "Fluorine in Pharmaceutical and Medicinal Chemistry: From Biophysical Aspects to Clinical Applications," eds. V. Gouverneur & K. Műller, Molecular Medicine and Medicinal Chemistry, vol. 6, chapter 12, pp 461-524, World Scientific Publishing Company, London, ISBN-13: 978-1848166349, 2012.

"Fluorocarbon agents for quantitative multimodal molecular imaging and targeted therapeutics." S. A. Wickline, R.P. Mason, S. D. Caruthers, J. Chen, P. M. Winter, M. S. Hughes, G. M. Lanza, pages 542-573, Chapter 35 in Molecular Imaging: Principles and Practice, R. Weissleder, S. S. Gambhir, B. D. Ross & A. Rehemtulla (Editors), People’s Medical Publishing House, 2010.

Non-invasive physiology and pharmacology using 19F magnetic resonance. J.X. Yu, W. Cui, D. Zhao, and R.P. Mason, chapter 5, In  Fluorine and Health, A. Tressaud & G. Haufe (Editors) May 2008 Elsevier B.V.

19F: a versatile reporter for non-invasive physiology and pharmacology using magnetic resonance. Yu, J.X., Kodibagkar V.D., Cui W., Mason R.P. Curr. Med. Chem. 2005 12 7 819-48.

Oxygen sensitive reporters

GdDO3NI, a nitroimidazole-based T 1 MRI contrast agent for imaging tumor hypoxia in vivo. Gulaka PK, Rojas-Quijano F, Kovacs Z, Mason RP, Sherry AD, Kodibagkar VD J. Biol. Inorg. Chem. 2013 Nov

Multimodality imaging of hypoxia in preclinical settings. Mason, R.P., Zhao D., Pacheco-Torres J., Cui W., Kodibagkar V.D., Gulaka P..K., Hao G., Thorpe P., Hahn E.W., Peschke P. Q J Nucl Med Mol Imaging 2010 Jun 54 3 259-80.

"GdDO3NI, a nitroimidazole-based T1 MR contrast agent for imaging tumor hypoxia in vivo."  P. K. Gulaka, F. Rojas-Quijano, Z. Kovacs, R.P. Mason, A. D. Sherry and V D. Kodibagkar, J. Bio. Inorg. Chem.,: 1–10 (2013) DOI 10.1007/s00775-013-1058-5

Quantitative tissue oxygen measurement in multiple organs using (19) F MRI in a rat model. Liu S., Shah S.J., Wilmes L.J., Feiner J., Kodibagkar V.D., Wendland M.F., Mason, R.P., Hylton N., Hopf H.W., Rollins M.D. Magnetic resonance in medicine: official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine 2011 Jun.

Proton imaging of siloxanes to map tissue oxygenation levels (PISTOL): a tool for quantitative tissue oximetry. Kodibagkar V.D., Wang X., Pacheco-Torres J., Gulaka P., Mason, R.P. NMR Biomed 2008 Oct 21 8 899-907.

Molecular imaging of hypoxia. Krohn K.A., Link J.M., Mason, R.P. J. Nucl. Med. 2008 Jun 49 Suppl 2 129S-48S.

Measuring changes in tumor oxygenation. Zhao D., Jiang L., Mason, R.P. Meth. Enzymol. 2004 386 378-418.

Near-infrared spectroscopy and imaging of tumor vascular oxygenation. Liu H., Gu Y., Kim J.G., Mason, R.P. Meth. Enzymol. 2004 386 349-78.

Enzyme activity reporters


Novel S-Gal® analogs as 1H MRI reporters for in vivo detection of β-galactosidase. P. K. Gulaka, J.X. Yu, L. Liu, R.P. Mason and V. D. Kodibagkar, Magn. Reson. Imaging 31(6):1006-1011 (2013).

Dual (19)F/(1)H MR gene reporter molecules for in Vivo detection of ß-Galactosidase. Yu, J.X., Kodibagkar V.D., Hallac R.R., Liu L., Mason, R.P. Bioconjug. Chem. 2012 Mar 23 3 596-603.


S-Gal, a novel 1H MRI reporter for beta-galactosidase. Cui W., Liu L., Kodibagkar V.D., Mason, R.P. Magn Reson Med 2010 Jul 64 1 65-71.

19F-NMR approach using reporter molecule pairs to assess beta-galactosidase in human xenograft tumors in vivo. Yu, J.X., Kodibagkar V.D., Liu L., Mason, R.P. NMR Biomed 2008 Aug 21 7 704-12.

19F-NMR detection of lacZ gene expression via the enzymic hydrolysis of 2-fluoro-4-nitrophenyl beta-D-galactopyranoside in vivo in PC3 prostate tumor xenografts in the mouse. Liu L., Kodibagkar V.D., Yu, J.X., Mason, R.P. FASEB J. 2007 Jul 21 9 2014-9.

Novel NMR platform for detecting gene transfection: synthesis and evaluation of fluorinated phenyl beta-D-galactosides with potential application for assessing LacZ gene expression. Yu J., Otten P., Ma Z., Cui W., Liu L., Mason, R.P. Bioconjug. Chem. 2004 Nov-Dec 15 6 1334-41

Optical Imaging

Oxygen-Sensing Chemiluminescent Iridium(III) 1,2-Dioxetanes: Unusual Coordination and Activity, H. N. Kagalwala, L. Bueno, H. Wanniarachchi, D. K. Unruh, K. B. Hamal, C. I. Pavlich, G. J. Carlson, K. G. Pinney, R. P. Mason, A. R. Lippert, Analysis & Sensing, October 2022 

Kinetics-Based Measurement of Hypoxia in Living Cells and Animals Using an Acetoxymethyl Ester Chemiluminescent Probe, L. S. Ryan, J. L. Gerberich, J. Cao, W. An, B. Jenkins, R. P. Mason, and A. R. Lippert, ACS Sens. 4, 5, 1391–1398, 2019

Kinetics-Based Measurement of Hypoxia in Living Cells and Animals Using an Acetoxymethyl Ester Chemiluminescent Probe, L. S. Ryan, J. L. Gerberich, J. Cao, W. An, B. Jenkins, R. P. Mason, and A. R. Lippert, ACS Sens. 4, 5, 1391–1398, 2019

Ratiometric pH imaging using a 1,2-dioxetane chemiluminescence resonance energy transfer sensor in live animals, L. Ryan, J. Gerberich, U. Haris, D. Nguyen, R.  Mason, A. Lippert,” ACS Sensors, 5, 9, 2925–2932 2020

Chemiluminescent 1,2-Dioxetane Iridium Complexes for Near-Infrared Oxygen Sensing, H. N. Kagalwala, J. Gerberich, C. Smith, R. P. Mason and A. R. Lippert, Angw. Chem.61 (12), e202115704

A Chemiluminescent Probe for HNO Quantification and Real-time Monitoring in Living Cells, W. An, L. S. Ryan, A. G. Reeves, K. J. Bruemmer, L. Mouhaffel, J. L. Gerberich, A. Winters, R. P. Mason, A. R. Lippert, Angw. Chem., 58 (5) 1361-1365 2019 DOI: 10.1002/ange.201811257

Energy transfer chemiluminescence for ratiometric pH imaging.  An W, Mason RP, Lippert AR.  Org Biomol Chem. 2018 May 22. doi: 10.1039/c8ob00972d. [Epub ahead of print]

Red-shifted emission from 1,2-dioxetane-based chemiluminescent reactions.Park JY, Gunpat J, Liu L, Edwards B, Christie A, Xie XJ, Kricka LJ, Mason RP Luminescence 2014 Sep 29 6 ii

Imaging beta-galactosidase activity in human tumor xenografts and transgenic mice using a chemiluminescent substrate. Liu L., Mason, R.P. PLoS ONE 2010 5 8 e12024.

Validating bioluminescence imaging as a high-throughput, quantitative modality for assessing tumor burden. Paroo Z., Bollinger R.A., Braasch D.A., Richer E., Corey D.R., Antich P.P., Mason, R.P. Mol Imaging 2004 Apr 3 2 117-24.


6-Trifluoromethylpyridoxine: novel (19)F NMR pH indicator for in vivo detection. Yu, J.X., Cui W., Bourke V.A., Mason, R.P. J. Med. Chem. 2012 Aug 55 15 6814-21.

"Development of novel 19F NMR pH indicators: Synthesis and evaluation of a series of fluorinated vitamin B6 analogs," S. He, R.P. Mason, S. Hunjan, V. D. Mehta, V. Arora, R. Katipally, P. V. Kulkarni, and P. P. Antich,  BioOrg. Med. Chem. 6, 1631-1639 (1998).

"Simultaneous intra- and extra-cellular pH measurement using 19F NMR of 6-Fluoropyridoxol." S. Hunjan, R.P. Mason, V. D. Mehta, P. V. Kulkarni, S. Aravind, V. Arora and P. P. Antich, Magn. Reson. Med., 39, 551-556 (1998).

"6-Fluoropyridoxal polymer conjugates: novel 19F pH indicators for magnetic resonance spectroscopy." V. D. Mehta, S. Aravind, P. V. Kulkarni, R.P. Mason, and P. P. Antich, Bioconj. Chem. 7, 536-540 (1996).

6-Fluoropyridoxol: a novel probe of cellular pH using 19F NMR spectroscopy." V. D. Mehta, P. V. Kulkarni, R.P. Mason, A. Constantinescu, S. Aravind, N. Goomer, and P. P. Antich, FEBS Letters, 349, 234-238 (1994).

"Fluorinated macromolecular probes for non-invasive assessment of pH by magnetic resonance spectroscopy." V. D. Mehta, P. V. Kulkarni, R.P. Mason, and P. P. Antich, BioMed. Chem. Letters, 3, 187-192 (1993).