Abstract
Rapid uptake of the calcium analog manganese (Mn2+) into spontaneous pituitary adenoma during MR imaging of aged rats generated the hypothesis that neuroendocrine tumors may have a corresponding increase in calcium influx required to trigger hormonal release. A goal of this study was to investigate the potential for clinical evaluation of pituitary adenoma by MR imaging combined with administration of Mn2+ (Mn-MR imaging). Mn-MR imaging was used to characterize the dynamic calcium influx in normal aged rat pituitary gland as well as spontaneous pituitary adenoma. To confirm the validity of Mn2+ as a calcium analog, we inhibited Mn2+ uptake into the olfactory bulb and pituitary gland of normal rats by using the calcium channel blocker verapamil. Rats with adenomas received fluorodeoxyglucose-positron-emission tomography (FDG-PET) scanning for characterization of tumor metabolism. Mn2+ influx was characterized in cultured pituitary adenoma cells. Volume of interest analysis of the normal aged pituitary gland versus adenoma indicated faster and increased calcium influx in adenoma at 1, 3, 11, and 48 hours. Mn2+ uptake into the olfactory bulb and pituitary gland of normal rats was inhibited by calcium channel blockers and showed dose-dependent inhibition on dynamic MR imaging. FDG-PET indicated correlation between tumor energy metabolism and Mn2+ influx as well as tumor size. These results indicate that adenomas have increased activity-dependent calcium influx compared with normal aged pituitary glands, suggesting a potential for exploitation in the clinical work-up of pituitary and other neuroendocrine tumors by developing Mn-MR imaging for humans.
Highlights
AND PURPOSE: Rapid uptake of the calcium analog manganese (Mn2ϩ) into spontaneous pituitary adenoma during MR imaging of aged rats generated the hypothesis that neuroendocrine tumors may have a corresponding increase in calcium influx required to trigger hormonal release
fluorodeoxyglucose–positron-emission tomography (FDG-PET) indicated correlation between tumor energy metabolism and Mn2ϩ influx as well as tumor size. These results indicate that adenomas have increased activity-dependent calcium influx compared with normal aged pituitary glands, suggesting a potential for exploitation in the clinical work-up of pituitary and other neuroendocrine tumors by developing Mn-MR imaging for humans
Pituitary adenomas may manifest clinically by hormonal hypersecretion, which is dependent on increased activity-dependent calcium influx.[15,16]
Summary
Mn-MR imaging was used to characterize the dynamic calcium influx in normal aged rat pituitary gland as well as spontaneous pituitary adenoma. Rats with adenomas received fluorodeoxyglucose–positron-emission tomography (FDG-PET) scanning for characterization of tumor metabolism. We performed in vivo MR imaging with MnCl2 to characterize the dynamic calcium influx in the normal aged rat pituitary gland as well as spontaneous pituitary adenomas in aged rats. To confirm the validity of Mn2ϩ as a calcium analog, we inhibited Mn2ϩ uptake into the olfactory bulb and pituitary gland of normal young rats by using the calcium channel blocker verapamil and assessed Mn2ϩ uptake by using. Aged rats with adenomas received additional scanning by using fluorodeoxyglucose–positron-emission tomography (FDG-PET) for further characterization of tumor glucose metabolism.
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