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

Abstract

The objective of this study was to evaluate the in vivo assay of folate receptors in nonfunctional pituitary adenomas using preoperative 99m Tc-folate SPECT/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 99m Tc-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 99m Tcfolate 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 99m Tc-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.

Contemporary Management of Clinically Non-functioning Pituitary Adenomas: A Clinical Review

“…32 Detection of FRα-expressing NFPA with 99mTc-Folate SPECT-CT helps in identifying tumours amenable to FRα-targeted therapy as demanded by the concept of personalized/precision cancer therapy which requires selection of patients for a specific targeted therapy based on molecular characterization of the tumour and its microenvironment. 98…”

Folate receptor overexpression can be visualized in real time during pituitary adenoma endoscopic transsphenoidal surgery with near-infrared imaging

“…Previous studies have demonstrated that NF pituitary adenomas overexpress FRa compared with functioning pituitary adenomas. 8,12 Immunohistochemical analysis was performed on paraffin-embedded tissue sections using murine monoclonal antibodies to FRa, sections were examined by a single neuropathologist (M.M.L. ), and H-scores (0-300) were determined ( Fig.…”

MANAGEMENT OF ENDOCRINE DISEASE: Present and future perspectives for medical therapy of nonfunctioning pituitary adenomas

“…Folate receptor-α targeted liposomal doxorubicin had antiproliferative, antiinvasive and proapoptotic activity in primary cell cultures derived from patients with NFPA (98), thus potentially being of value for treating aggressive tumors. FR-α-expressing NFPA can be detected with 99m Tc-Folate SPECT-CT, thus identifying tumors amenable to folate receptor-targeted therapy (99).…”