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.
Tumor fluorescence 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 2.3 mm. 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.