18F-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′- 18 F-fluorothymidine ( 18 F-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 18 F-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 18 F-FLT uptake in the pelvis were considered to have hypoplastic MDS (hypo-MDS). 18 F-FLT PET and diffusion-weighted imaging (DWI) were visually and quantitatively evaluated. Results The 18 F-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 18 F-FLT according to disease severity. Multiple 18 F-FLT foci were observed in the proximal extremities, and they were in the central skeleton in severe AA patients. Post-treatment 18 F-FLT PET scans of severe AA patients reflected the response of hematopoietic activity to treatment. MDS patients had marked 18 F-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. 18 F-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 18 F-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 18 F-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 18 F-FLT PET. 18 F-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 o...

Fluorothymidine Positron Emission Tomography (FLT-PET) Repeatability and Response Evaluation in Advanced Pancreatic Cancer Patients Treated with Gemcitabine-Based Chemotherapy

“…An increased uptake in vertebral body uptake 3 to 4 weeks after chemotherapy was indicative of increased proliferative activity consequent to marrow recovery after chemotherapy, as was also observed in other studies [35,36]. An increase in the splenic FLT uptake paralleled that in the vertebral body; this is more likely to reflect the FLT activity in the blood pool, although a potential role in haematopoiesis cannot be completely ruled out without corroborative tissue data.…”

The value of bone marrow, liver, and spleen imaging in diagnosis, prognostication, and follow-up monitoring of myeloproliferative neoplasms: a systematic review

“…Regarding the etiology of splenomegaly, a study using 99m Tc-red blood cell (RBC) and 113m In-heat-damaged RBC scintigraphy demonstrated a significant correlation between splenic size and hypervascularization in both MF and PV, whilst a correlation with hypercellularity was only seen in MF [ 71 ]. In line with these findings, variably increased splenic uptake of 18 F-FDG, 18 F-FLT and 111 In-Cl3 has been demonstrated in MF, often combined with low axial and/or high peripheral BM uptake [ 27 , 28 , 30 , 35 – 39 ]. Lastly, increased splenic membrane metabolism was suspected in one PV and three MF patients because of increased phosphomonoester/Pi and phosphomonoester/B-ATP ratios as measured by splenic 31-phosphor MRS [ 72 ].…”

“…Dixon quantitatively confirmed markedly decreased fat fractions in a few patients [ 33 , 34 ]. Diffusion-weighted MRI showed increased BM signals in two patients [ 35 ]. On short-tau inversion recovery (STIR) images, skeletal signals ranged from high tot low [ 8 , 31 , 32 ], and were presumed to reflect the degree of cellularity [ 31 ].…”

“…In analogy to PV, 18 F-FDG PET/CT showed high axial BM uptake with variable degrees of peripheral BM uptake in MF patients [ 36 ]. In contrast, distribution patterns on 18 F-FLT PET/CT ranged from near-normal to decreased axial uptake with peripheral BM expansion [ 35 , 37 , 38 ]. Axial uptake of 111 In-Cl3 and 99m Tc-colloid as detected by scintigraphy were mostly normal or low [ 27 , 28 , 30 , 38 – 44 ], whilst high peripheral BM uptake was common [ 27 , 28 , 30 , 38 – 42 ].…”

Integrated [18F]FDG PET/MRI demonstrates the iron-related bone-marrow physiology

“…[ 18 F]FDG PET reveals glycolytic activity, DWI reflects the restricted random movement of extra-cellular water protons (cellular density), PDFF measurements assess the fat content, and R2* reflects the level of iron deposition. The recent introduction of integrated PET/MRI has enabled simultaneous whole-body bone-marrow PET and functional MR imaging in bone-marrow disorders 5 , 6 . Therefore, physiological factors influencing bone-marrow [ 18 F]FDG uptake and MR signals and the associations should be clarified for accurate diagnosis.…”