[18F]FDG and [18F]FES positron emission tomography for disease monitoring and assessment of anti-hormonal treatment eligibility in granulosa cell tumors of the ovary

Abstract

Purpose: Adult granulosa cell tumors (AGCTs) of the ovary represent a rare malignancy in which timing and choice of treatment is a clinical challenge. This study investigates the value of FDG-PET/CT and FES-PET/CT in monitoring recurrent AGCTs and assessing eligibility for anti-hormonal treatment.Materials and Methods: We evaluated 22 PET/CTs from recurrent AGCT patients to determine tumor FDG (n = 16) and FES (n = 6) uptake by qualitative and quantitative analysis. We included all consecutive patients from two tertiary hospitals between 2003-2020. Expression of ERα and ERβ and mitoses per 2 mm 2 were determined by immunohistochemistry and compared to FES and FDG uptake, respectively.Results: Qualitative assessment showed low-to-moderate FDG uptake in most patients (14/16), and intense uptake in 2/16. One patient with intense tumor FDG uptake had a high mitotic rate (18 per 2 mm 2 ) Two out of six patients showed FES uptake on PET/CT at qualitative analysis. Lesion-based quantitative assessment showed a mean SUV max of 2.4 (± 0.9) on FDG-PET/CT and mean SUV max of 1.7 (± 0.5) on FES-PET/CT. Within patients, expression of ERα and ERβ varied and did not seem to correspond with FES uptake. In one FES positive patient, tumor locations with FES uptake remained stable or decreased in size during anti-hormonal treatment, while all FES negative locations progressed.Conclusions: This study shows that in AGCTs, FDG uptake is limited and therefore FDG-PET/CT is not advised. FES-PET/CT may be useful to non-invasively capture the estrogen receptor expression of separate tumor lesions and thus assess the potential eligibility for hormone treatment in AGCT patients.

The Application of 18F-FES PET in Clinical Cancer Care

“…All studies were published between 1995 and 2022, 6,7,10-14,18-53 of which 29 (63%) were prospective. 6,7,[10][11][12][13][14][18][19][20][21][23][24][25][26][27][28][29]34,36,[43][44][45][46][47][48][49][50][51] Of the 43 studies, 32 (74%) were on breast cancer, 6,7,[18][19][20][21][22][23][24][25][26]28,31,[33][34][35][37][38][39][40][41][43][44]…”

“…Of the 43 included studies, 28 (63%) conducted FES PET imaging to detect ER expression on malignant lesions, 6,7,[10][11][12][20][21][22][23][24][25][27][28][29][31][32][33][34][35][36][37][38][39][40][41]46,52 and 12 (28%) 13,24,39,41,42,[45][46][47][48][49][50][51] and 4 (9%) 14,43,44,53 studies conducted FES PET imaging, respectively, to predict and monitor the treatment response (such as endocrine therapy or chemotherapy), progressionfree survival (PFS), and overall survival (OS) (Table 1).…”

“…Mankoff et al 18 noted that the rapid clearance of FES and its metabolite background was nearly constant, and imaging starting 20 to 30 minutes after the injection may provide good visualization of estrogencontaining tissues. Furthermore, the median of the mean/median uptake interval between radiotracer administration and scan acquisition for the FES radiotracer was 60 minutes (range, 30-110 minutes) in most of the included studies 6,7,[10][11][12][13][14]19,[22][23][24][26][27][28][29][30][31][32][33][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][51][52][53] (Supplement Table 1, Supplemental Digital Content, http://links.lww.com/ CNM/A425).…”

“…In 26 studies (60%), both FES and FDG PET were used for imaging. 7,10,12,13,[21][22][23][24][27][28][29][30]32,33,36,[40][41][42][43][44][46][47][48][51][52][53] Immunohistochemistry staining in biopsy samples was used as criterion standard for confirming ER positivity in 27 studies (63%), 6,7,[10][11][12][13][14]20,21,24,25,27,[32][33][34]36,37,40,42,[45][46][47][48][49][50]…”

“…In 20 studies, FES uptake was estimated by SUV max, 11,14,20-23,27, 30,35,37,39,[43][44][45][46][48][49][50][51][52] and 14 studies were estimated by SUV mean 7,10,12, [24][25][26][27]29,32,41,42,46,47,53 (Supplement Table 2, Supplemental Digital Content, http://links.lww.com/CNM/A425).…”