In vivo manganese MR imaging of calcium influx in spontaneous rat pituitary adenoma.
OBJECTIVE
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).


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.


CONCLUSIONS
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.
Cross
D J
DJ
Washington National Regional Primate Center, University of Washington, Seattle, WA 98195-7115, USA.
Flexman
J A
JA
Anzai
Y
Y
Sasaki
T
T
Treuting
P M
PM
Maravilla
K R
KR
Minoshima
S
S
D000375:Aging / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003287:Contrast Media; D004305:Dose-Response Relationship, Drug; D019788:Fluorodeoxyglucose F18; D013006:Growth Hormone / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008345:Manganese; D010902:Pituitary Gland / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology; D049268:Positron-Emission Tomography; D015175:Prolactinoma / Q000378:metabolism; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D003287:Contrast Media; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D008345:Manganese; D013006:Growth Hormone; D014700:Verapamil; D002118:Calcium