Application of 18F-Fapi PET/MRI in the Assessment of Myelofibrosis: A Multi-Center Prospective Observational Study

Introduction

Myelofibrosis (MF) is a myeloproliferative disorder characterized by the replacement of hematopoietic cells in the bone marrow (BM) with fibrous tissue. This condition leads to abnormal red blood cell morphology, anemia, and splenomegaly. While 18F-FDG PET imaging has been used to assess MF, it is less effective for evaluating high-grade MF because fluorine-18-fluorodeoxyglucose uptake decreases as bone marrow fibrosis progresses. Fibroblast activation protein (FAP) is a serine protease predominantly expressed in fibroblasts, often overexpressed in cancer-associated fibroblasts and pathological conditions like myelofibrosis. FAP inhibitors (FAPI), labeled with 18F, can be used as tracers in PET imaging to detect areas of FAP expression. This study aims to evaluate the performance of 18F-FAPI PET/MRI in assessing MF and compare it with 18F-FDG PET/CT imaging.

Materials and Methods

This multi-center prospective observational study (NCT06164561) enrolled 26 patients with MF from April 2022 to June 2024. The cohort included 11 cases of primary MF, 11 of myelodysplastic syndrome with MF, 2 of chronic myelomonocytic leukemia with MF, and 2 of acute myeloid leukemia with MF. Two scoring methods were used to assess the distribution and density of MF throughout the body on the PET maximum intensity projection (MIP) images:

1. A previously reported grading system from 18F-FDG PET/CT imaging.
2. A newly designed scoring system, dividing the skeleton into six regions: sternum/ribs/scapula, spine, pelvis, humerus/femur, tibia/fibula, and metacarpals/phalanges of the foot. Each region is scored by uptake density: the bone uptake was compared with adjacent soft tissue uptake (SUVmean),a score of 0 was assigned if the uptake was lower than or equal to the surrounding soft tissue, of 1 if slightly increased (>1 and ≤2), and 2 if significantly higher (>2). The total score was the sum of all regional scores.

Imaging grades or scores were compared with myelofibrosis pathology grades using PASW Statistics 18 software for Pearson or Spearman correlation analysis. A p-value <0.05 was considered statistically significant.

Results

1. Comparison with Pathology Grades: Patients were divided into two subgroups based on BMF pathology grades: Grade 0-1 (n=8) and Grade 2-3 (n=18). The 18F-FAPI score was higher in the high-grade group compared to the low-grade group (6.06±3.49 vs. 2.14±2.27, P<0.05). Pathologic grades positively correlated with 18F-FAPI grades and scores (both P<0.05) but showed no significant correlation with 18F-FDG grades or scores (both P>0.05).
2. Splenic Involvement: 18F-FAPI imaging provided better visualization of splenic involvement than 18F-FDG imaging. The 18F-FAPI score correlated positively with spleen volume and uptake (P<0.05), while 18F-FDG did not show significant correlations (P>0.05).

Conclusion

1. Our data indicate that 18F-FAPI imaging is more comparable to pathology grades of BMF than 18F-FDG and positively correlates with spleen volume and uptake.
2. The scoring system used in this study offers a more precise assessment of both the density and distribution of MF throughout the body compared to the previously used grading system.

This study represents the first application of 18F-FAPI PET/MRI in assessing MF. Our findings suggest that imaging could potentially replace bone marrow biopsy as a non-invasive method for evaluating myelofibrosis, covering both density and distribution. Additionally, 18F-FAPI PET/MRI accurately assessed extramedullary MF involvement, such as in the spleen, which is typically not accessible for biopsy. Further prospective studies with larger sample sizes are needed to validate these findings.