68Ga-FAPI as a Diagnostic Tool in Sarcoma: Data from the 68Ga-FAPI PET Prospective Observational Trial

Abstract

Bone and soft-tissue sarcomas express fibroblast activation protein (FAP) on tumor cells and associated fibroblasts. Therefore, FAP is a promising therapeutic and diagnostic target. Novel radiolabeled FAP inhibitors (e.g., 68Ga-FAPI-46) have shown high tumor uptake on PET in sarcoma patients. Here, we report the endpoints of the 68Ga-FAPI PET prospective observational trial. Methods: Forty-seven patients with bone or soft-tissue sarcomas undergoing clinical 68Ga-FAPI PET were eligible for enrollment into the 68Ga-FAPI PET observational trial. Of these patients, 43 also underwent 18F-FDG PET. The primary study endpoint was the association between 68Ga-FAPI PET uptake intensity and histopathologic FAP expression analyzed with Spearman r correlation. Secondary endpoints were detection rate, positive predictive value (PPV), interreader reproducibility, and change in management. Datasets were interpreted by 2 masked readers. Results: The primary endpoint was met, and the association between 68Ga-FAPI PET uptake intensity and histopathologic FAP expression was significant (Spearman r = 0.43; P = 0.03). By histopathologic validation, PPV was 1.00 (95% CI, 0.87-1.00) on a per-patient and 0.97 (95% CI, 0.84-1.00) on a per-region basis. In cases with histopathologic validation, 27 of 28 (96%) confirmed patients and 32 of 34 (94%) confirmed regions were PET-positive, resulting in an SE of 0.96 (95% CI, 0.82-1.00) on a per-patient and 0.94 (95% CI, 0.80-0.99) on a per-region basis. The detection rate on a per-patient basis in 68Ga-FAPI and 18F-FDG PET was 76.6% and 81.4%, respectively. In 8 (18.6%) patients, 68Ga-FAPI PET resulted in an upstaging compared with 18F-FDG PET. 68Ga-FAPI PET readers showed substantial to almost perfect agreement for the defined regions (Fleiss κ: primary κ = 0.78, local nodal κ = 0.54, distant nodal κ = 0.91, lung κ = 0.86, bone κ = 0.69, and other κ = 0.65). Clinical management changed in 13 (30%) patients after 68Ga-FAPI PET. Conclusion: We confirm an association between tumoral 68Ga-FAPI PET uptake intensity and histopathologic FAP expression in sarcoma patients. Further, with masked readings and independent histopathologic validation, 68Ga-FAPI PET had a high PPV and sensitivity for sarcoma staging.

Keywords: FAPI; PET; cancer imaging; fibroblast activation protein; sarcoma.

© 2022 by the Society of Nuclear Medicine and Molecular Imaging.

Figures

Graphical abstract

FIGURE 1.

Enrollment flowchart.

FIGURE 2.

Primary endpoint: association between 68Ga-FAPI PET uptake intensity and FAP immunohistochemistry (IHC) score. (A) 68Ga-FAPI SUVmax by immunohistochemistry score, with positive correlation (r = 0.43, P < 0.05). (B) 68Ga-FAPI SUVmax for patients separated into high-grade and low-grade groups and patients with tumor entities for which grading does not apply. Uptake does not significantly differ between groups (P = 0.49).

FIGURE 3.

Case presentation: 69-y-old patient with metastatic low-grade myofibroblastic sarcoma. (A–D) Images of primary tumor of dorsal left thigh show higher uptake with 68Ga-FAPI (SUVmax, 34.5; A and B) than with 18F-FDG (SUVmax, 20.6; C and D). Shown are maximum-intensity-projection PET images (A and D), axial CT images (B and C, top), and axial PET images (B and C, bottom). (E and F) Primary lesion (arrow) demonstrated high FAP expression on immunohistochemistry (E), compared with negative immunohistochemistry seen in different patient (F).

FIGURE 4.

Change in management. (A) pie chart of implemented management change after FAPIPET for 44 patients. Types of changes were categorized as no change, minor change (e.g. modification of systemic or local treatment), major change (e.g. treatment shift towards local or systemic therapy) and no report of implementation of intended treatment. (B) shows the types of major change after FAPI-PET in 7 patients. Major shift towards systemic therapy were noted most often.