Early assessment of treatment response in patients with AML using [(18)F]FLT PET imaging.

Assessment of treatment response in acute leukemia is routinely performed after therapy via bone marrow biopsy. We investigated the use of positron emission tomography (PET) for early assessment of treatment response in patients with acute myeloid leukemia (AML), using the proliferation marker 3'-deoxy-3'-[(18)F]fluoro-l-thymidine (FLT). Eight adult AML patients receiving induction chemotherapy underwent whole-body FLT PET/CT scans acquired at different time points during therapy. Patients who entered complete remission (CR) exhibited significantly lower FLT uptake in bone marrow than those patients with resistant disease (RD). In bone marrow, mean and maximum standardized uptake values were 0.8, 3.6 for CR and 1.6, 11.4 for RD, p<0.001. FLT PET results for CR and RD patients were independent of assessment time point, suggesting that FLT PET scans acquired as early as 2 days after chemotherapy initiation may be predictive of clinical response. This pilot study suggests that FLT PET imaging during induction chemotherapy may serve as an early biomarker of treatment response in AML.

[1]  T. Mattfeldt,et al.  Early assessment of therapy response in malignant lymphoma with the thymidine analogue [18F]FLT , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[2]  Wei Chen,et al.  Predicting treatment response of malignant gliomas to bevacizumab and irinotecan by imaging proliferation with [18F] fluorothymidine positron emission tomography: a pilot study. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  V. Devita,et al.  Cancer : Principles and Practice of Oncology , 1982 .

[4]  C. Bloomfield,et al.  Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  Thomas Kull,et al.  First Demonstration of Leukemia Imaging with the Proliferation Marker 18F-Fluorodeoxythymidine , 2008, Journal of Nuclear Medicine.

[6]  Falko Fend,et al.  Early Response Assessment Using 3′-Deoxy-3′-[18F]Fluorothymidine-Positron Emission Tomography in High-Grade Non-Hodgkin's Lymphoma , 2007, Clinical Cancer Research.

[7]  W. Hiddemann,et al.  Early blast clearance by remission induction therapy is a major independent prognostic factor for both achievement of complete remission and long-term outcome in acute myeloid leukemia: data from the German AML Cooperative Group (AMLCG) 1992 Trial. , 2003, Blood.

[8]  M. Melamed,et al.  Bone marrow cell count per cubic millimeter bone marrow: a new parameter for quantitating therapy-induced cytoreduction in acute leukemia. , 1982, Blood.

[9]  Mark Muzi,et al.  In vivo validation of 3'deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) as a proliferation imaging tracer in humans: correlation of [(18)F]FLT uptake by positron emission tomography with Ki-67 immunohistochemistry and flow cytometry in human lung tumors. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[10]  Francis R Verdun,et al.  Performance comparison of two commercial BGO-based PET/CT scanners using NEMA NU 2-2001. , 2007, Medical physics.

[11]  U. Haberkorn,et al.  A new precursor for the radiosynthesis of [18F]FLT. , 2002, Nuclear medicine and biology.

[12]  H. Malcolm Hudson,et al.  Accelerated image reconstruction using ordered subsets of projection data , 1994, IEEE Trans. Medical Imaging.

[13]  E. Vellenga,et al.  18F-FLT PET in hematologic disorders: a novel technique to analyze the bone marrow compartment. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[14]  O. Muzik,et al.  Kinetics of 3'-deoxy-3'-[F-18]fluorothymidine uptake and retention in dogs. , 2002, Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging.

[15]  Otto Muzik,et al.  Imaging proliferation in vivo with [F-18]FLT and positron emission tomography , 1998, Nature Medicine.

[16]  G Flandrin,et al.  Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. , 1985, Annals of internal medicine.

[17]  A. Shields,et al.  PET imaging with 18F-FLT and thymidine analogs: promise and pitfalls. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[18]  Eric O. Aboagye,et al.  Imaging early changes in proliferation at 1 week post chemotherapy: a pilot study in breast cancer patients with 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography , 2007, European Journal of Nuclear Medicine and Molecular Imaging.

[19]  Michael E. Phelps,et al.  Usefulness of 3′-[F-18]Fluoro-3′-deoxythymidine with Positron Emission Tomography in Predicting Breast Cancer Response to Therapy , 2005, Molecular Imaging and Biology.