In Vivo Assay of Folate Receptors in Nonfunctional Pituitary Adenomas with 99mTc-Folate SPECT/CT

The objective of this study was to evaluate the in vivo assay of folate receptors in nonfunctional pituitary adenomas using preoperative Tc-99m-folate SPEC/CT and Western blot analysis (WBA) of surgical specimens as the standard. Methods: Fifty-six patients (29 men, 27 women; age range, 29-82 y) with clinically nonfunctional pituitary adenomas on MRI underwent preoperative imaging using 666 MBq (18 mCi) of Tc-99m-folate. SPECT/CT images and whole-body and lateral head planar images were acquired approximately 2 h after injection. Surgical resection took place within a week. WBA on a portion of the excised specimens assessed folate receptor expression in 49 patients. Attenuation-corrected Tc-99m-folate SPECT/CT images were assessed qualitatively and quantitatively (maximal adenoma counts to background), with WBA as a standard. Results: Integrated CT was useful for uptake localization and assisted region-of-interest placement. Qualitative interpretation of planar imaging yielded a sensitivity of 81% and specificity of 72%. Qualitative SPECT/CT yielded a sensitivity of 94% and specificity of 61%. Receiver-operating-characteristic curve analysis of quantitative uptake yielded a tumor-to-background cutoff ratio of 3.5, with a sensitivity of 81% and specificity of 83%. Scalp uptake yielded consistent results (over the brain, neck, and choroid plexus) for background when SPECT/CT misalignment artifacts were avoided. Detection of pituitary uptake on anterior-posterior and lateral images was hampered by facial uptake, which varied between patients. Conclusion: SPECT/CT of Tc-99m-folate is an accurate method of assaying folate receptors in vivo and may provide a quantitative marker for identifying folate receptor-positive tumors. This method may also prove beneficial in selecting patients for folate-targeted therapy of clinically nonfunctional pituitary adenomas, for which there is currently no medical therapy.