In vivo fluorescence imaging and urinary monoamines as surrogate biomarkers of disease progression in a mouse model of pheochromocytoma

Martin Ullrich, Ralf Bergmann, Mirko Peitzsch, Marc Cartellieri, Nan Qin, Monika Ehrhart-Bornstein, Norman L. Block, Andrew V. Schally, Jens Pietzsch, Graeme Eisenhofer, Stefan R. Bornstein, Christian G. Ziegler

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Pheochromocytoma (PHEO) is a rare but potentially lethal neuroendocrine tumor arising from catecholamine-producing chromaffin cells. Especially for metastatic PHEO, the availability of animal models is essential for developing novel therapies. For evaluating therapeutic outcome in rodent PHEO models, reliable quantification of multiple organ lesions depends on dedicated small-animal in vivo imaging, which is still challenging and only available at specialized research facilities. Here, we investigated whether whole-body fluorescence imaging and monitoring of urinary free monoamines provide suitable parameters for measuring tumor progression in a murine allograft model of PHEO.We generated an mCherry-expressing mouse PHEO cell line by lentiviral gene transfer. These cells were injected subcutaneously into nude mice to perform whole-body fluorescence imaging of tumor development. Urinary free monoamines were measured by liquid chromatography with tandem mass spectrometry.Tumorfluorescence intensity and urinary outputs of monoamines showed tumor growth-dependent increases (P < .001) over the 30 days of monitoring post-tumor engraftment. Concomitantly, systolic blood pressure was increased significantly during tumor growth. Tumor volume correlated significantly (P < .001) and strongly with tumor fluorescence intensity (rs = 0.946), and urinary outputs of dopamine (rs = 0.952), methoxytyramine (rs = 0.947), norepinephrine (rs = 0.756), and normetanephrine (rs = 0.949). Dopamine and methoxytyramine outputs allowed for detection of lesions at diameters below 2.3mm.Our results demonstrate that mouse pheochromocytoma (MPC)-mCherry cell tumors are functionally similar to human PHEO. Both tumor fluorescence intensity and urinary outputs of free monoamines provide precise parameters of tumor progression in this sc mouse model of PHEO. This animal model will allow for testing new treatment strategies for chromaffin cell tumors.

Original languageEnglish (US)
Pages (from-to)4149-4156
Number of pages8
JournalEndocrinology
Volume155
Issue number11
DOIs
StatePublished - Nov 1 2014

ASJC Scopus subject areas

  • Endocrinology

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    Ullrich, M., Bergmann, R., Peitzsch, M., Cartellieri, M., Qin, N., Ehrhart-Bornstein, M., Block, N. L., Schally, A. V., Pietzsch, J., Eisenhofer, G., Bornstein, S. R., & Ziegler, C. G. (2014). In vivo fluorescence imaging and urinary monoamines as surrogate biomarkers of disease progression in a mouse model of pheochromocytoma. Endocrinology, 155(11), 4149-4156. https://doi.org/10.1210/en.2014-1431