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AJNR - American Journal of Neuroradiology

Published ahead of print on October 9, 2007
doi: 10.3174/ajnr.A0693

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American Journal of Neuroradiology 28:1865-1871, November-December 2007
© 2007 American Society of Neuroradiology

FUNCTIONAL

In Vivo Manganese–MR Imaging of Calcium Influx in Spontaneous Rat Pituitary Adenoma

D.J. Cross^a,e, J.A. Flexman^c, Y. Anzai^b, T. Sasaki^b, P.M. Treuting^d, K.R. Maravilla^b and S. Minoshima^a,b,c,e

^a Washington National Regional Primate Center, University of Washington, Seattle, Wash
^b Department of Radiology, University of Washington, Seattle, Wash
^c Department of Bioengineering, University of Washington, Seattle, Wash
^d Department of Comparative Medicine, University of Washington, Seattle, Wash
^e Neuroscience Program, University of Michigan, Ann Arbor, Mich

Please address correspondence to Satoshi Minoshima, MD, PhD, Department of Radiology, University of Washington, 1959 NE Pacific St, BB201c, Box 357115, Seattle, WA 98195-7115; e-mail: minoshim{at}u.washington.edu

BACKGROUND AND PURPOSE: 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).

MATERIALS AND METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

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