18 F-FLT PET/MRI for bone marrow failure syndrome-initial experience

Abstract

Background

Bone marrow failure syndrome (BMFS) is a heterogeneous group of disorders associated with single- or multiple-lineage cytopenia and failure of normal hematopoiesis. We assessed the feasibility of integrated PET/MRI with 3′-deoxy-3′-¹⁸F-fluorothymidine (¹⁸F-FLT) to assess the pathophysiology of whole-body bone marrow for the diagnosis and monitoring of BMFS. Twenty-five consecutive patients with BMFS underwent a pre-treatment ¹⁸F-FLT PET/MRI scan. They included 7 patients with aplastic anemia (AA), 16 with myelodysplastic syndrome (MDS), and 2 with myeloproliferative neoplasms (MPNs), primary myelofibrosis (MF), and secondary [post-essential thrombocythemia (post-ET)] MF. Two of the seven AA patients underwent a post-treatment scan. Eight of the 16 MDS patients who exhibited decreased ¹⁸F-FLT uptake in the pelvis were considered to have hypoplastic MDS (hypo-MDS). ¹⁸F-FLT PET and diffusion-weighted imaging (DWI) were visually and quantitatively evaluated.

Results

The ¹⁸F-FLT uptake in the ilium was strongly correlated with bone marrow cellularity based on biopsy samples (ρ = 0.85). AA patients exhibited heterogeneously decreased uptake of ¹⁸F-FLT according to disease severity. Multiple ¹⁸F-FLT foci were observed in the proximal extremities, and they were in the central skeleton in severe AA patients. Post-treatment ¹⁸F-FLT PET scans of severe AA patients reflected the response of hematopoietic activity to treatment. MDS patients had marked ¹⁸F-FLT uptake in the central skeleton and proximal extremities, whereas hypo-MDS patients had heterogeneously decreased uptake, similar to that of non-severe AA patients. ¹⁸F-FLT PET and DWI were unable to predict the progression to leukemia for both MDS and hypo-MDS patients. A primary MF patient had slightly decreased ¹⁸F-FLT uptake in the central skeleton, but marked expansion of bone marrow activity to the distal extremities and high uptake of tracer in the extremely enlarged spleen (extramedullary hematopoiesis). In contrast, a secondary (post-ET) MF patient demonstrated marked bone marrow uptake, reflecting the hypercellular marrow with fibrosis. DWI revealed diffusely high signal intensities in both the primary and secondary MF patients.

Conclusion

¹⁸F-FLT PET can be used to noninvasively assess whole-body bone marrow proliferative activity and DWI may reflect the different aspects of bone marrow pathophysiology from ¹⁸F-FLT PET. ¹⁸F-FLT PET/MRI is useful for the diagnosis and monitoring of BMFS, except for the differentiation between non-severe AA and hypo-MDS, and the prediction of progression to leukemia.

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