Abstract

This report describes a multimodal whole-body 3′-deoxy-3′[(18)F]-fluorothymidine positron emission tomography (FLT-PET) and dual-energy computed tomography (DECT) method to identify leukemia distribution within the bone marrow environment (BME) and to develop disease- and/or BME-specific radiation strategies. A control participant and a newly diagnosed patient with acute myeloid leukemia prior to induction chemotherapy were scanned with FLT-PET and DECT. The red marrow (RM) and yellow marrow (YM) of the BME were segmented from DECT using a basis material decomposition method. Functional total marrow irradiation (fTMI) treatment planning simulations were performed combining FLT-PET and DECT imaging to differentially target irradiation to the leukemia niche and the rest of the skeleton. Leukemia colonized both RM and YM regions, adheres to the cortical bone in the spine, and has enhanced activity in the proximal/distal femur, suggesting a potential association of leukemia with the BME. The planning target volume was reduced significantly in fTMI compared with conventional TMI. The dose to active disease (standardized uptake value >4) was increased by 2-fold, while maintaining doses to critical organs similar to those in conventional TMI. In conclusion, a hybrid system of functional–anatomical–physiological imaging can identify the spatial distribution of leukemia and will be useful to both help understand the leukemia niche and develop targeted radiation strategies.

Highlights

  • Total marrow irradiation (TMI) with helical tomotherapy or volumetric-modulated arc therapy is a sophisticated technique for conditioning before hematopoietic cell transplantation.[1,2,3]

  • We recently reported on the use of whole body (WB) dual-energy computed tomography (DECT) to reveal a skeletal-wide heterogeneity within red marrow (RM) and yellow marrow (YM) composition, and the TMI irradiation technique was proposed for targeting specific bone marrow environment (BME) regions, offering a significant dose reduction to critical organs.[10]

  • We present a novel hybrid WB fluorothymidine positron emission tomography (FLT-PET)-DECT imaging strategy to identify the spatial distribution of leukemia and its association with the BME

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Summary

Introduction

Total marrow irradiation (TMI) with helical tomotherapy or volumetric-modulated arc therapy is a sophisticated technique for conditioning before hematopoietic cell transplantation.[1,2,3] Total marrow irradiation focuses radiation to the entire skeletal anatomy albeit with the simplified premise that hematologic disease is distributed homogeneously in the bone marrow (BM). AML indicates acute myelogenous leukemia; CT, computed tomography; FLT, 30-deoxy-30[(18)F]-fluorothymidine; PET, positron emission tomography; SUV, standardized uptake value.

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