Evaluation of limited blood sampling population input approaches for kinetic quantification of [18F]fluorothymidine PET data

BackgroundQuantification of kinetic parameters of positron emission tomography (PET) imaging agents normally requires collecting arterial blood samples which is inconvenient for patients and difficult to implement in routine clinical practice. The aim of this study was to investigate whether a population-based input function (POP-IF) reliant on only a few individual discrete samples allows accurate estimates of tumour proliferation using [18F]fluorothymidine (FLT).MethodsThirty-six historical FLT-PET data with concurrent arterial sampling were available for this study. A population average of baseline scans blood data was constructed using leave-one-out cross-validation for each scan and used in conjunction with individual blood samples. Three limited sampling protocols were investigated including, respectively, only seven (POP-IF7), five (POP-IF5) and three (POP-IF3) discrete samples of the historical dataset. Additionally, using the three-point protocol, we derived a POP-IF3M, the only input function which was not corrected for the fraction of radiolabelled metabolites present in blood. The kinetic parameter for net FLT retention at steady state, Ki, was derived using the modified Patlak plot and compared with the original full arterial set for validation.ResultsSmall percentage differences in the area under the curve between all the POP-IFs and full arterial sampling IF was found over 60 min (4.2%-5.7%), while there were, as expected, larger differences in the peak position and peak height.A high correlation between Ki values calculated using the original arterial input function and all the population-derived IFs was observed (R2 = 0.85-0.98). The population-based input showed good intra-subject reproducibility of Ki values (R2 = 0.81-0.94) and good correlation (R2 = 0.60-0.85) with Ki-67.ConclusionsInput functions generated using these simplified protocols over scan duration of 60 min estimate net PET-FLT retention with reasonable accuracy.

[1]  T. Coleman,et al.  On the Convergence of Reflective Newton Methods for Large-scale Nonlinear Minimization Subject to Bounds , 1992 .

[2]  D. Visvikis,et al.  Comparison of methodologies for the in vivo assessment of 18FLT utilisation in colorectal cancer , 2004, European Journal of Nuclear Medicine and Molecular Imaging.

[3]  Floris H. P. van Velden,et al.  Image derived input functions for dynamic High Resolution Research Tomograph PET brain studies , 2008, NeuroImage.

[4]  D. Mankoff,et al.  A graphical analysis method to estimate blood-to-tissue transfer constants for tracers with labeled metabolites. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[5]  Roger N Gunn,et al.  Parametrically defined cerebral blood vessels as non-invasive blood input functions for brain PET studies. , 2004, Physics in medicine and biology.

[6]  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.

[7]  Dong Soo Lee,et al.  Kinetic Modeling of 3′-Deoxy-3′-18F-Fluorothymidine for Quantitative Cell Proliferation Imaging in Subcutaneous Tumor Models in Mice , 2008, Journal of Nuclear Medicine.

[8]  Klaus Wienhard,et al.  Noninvasive quantification of 18F-FLT human brain PET for the assessment of tumour proliferation in patients with high-grade glioma , 2009, European Journal of Nuclear Medicine and Molecular Imaging.

[9]  M. Bentourkia,et al.  Kinetic modeling of PET data without blood sampling , 2005, IEEE Transactions on Nuclear Science.

[10]  G. Watkins,et al.  Kinetic Analysis of 3′-Deoxy-3′-18F-Fluorothymidine (18F-FLT) in Head and Neck Cancer Patients Before and Early After Initiation of Chemoradiation Therapy , 2009, Journal of Nuclear Medicine.

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

[12]  Cyril Riddell,et al.  Noninvasive estimation of the aorta input function for measurement of tumor blood flow with [/sup 15/O] water , 2001, IEEE Transactions on Medical Imaging.

[13]  V. Dhawan,et al.  Noninvasive quantitative fluorodeoxyglucose PET studies with an estimated input function derived from a population-based arterial blood curve. , 1993, Radiology.

[14]  T. Mattfeldt,et al.  Molecular imaging of proliferation in malignant lymphoma. , 2006, Cancer research.

[15]  R. Boellaard,et al.  Reproducibility of quantitative 18F-3′-deoxy-3′-fluorothymidine measurements using positron emission tomography , 2009, European Journal of Nuclear Medicine and Molecular Imaging.

[16]  Stephen L Bacharach,et al.  Simplified kinetic analysis of tumor 18F-FDG uptake: a dynamic approach. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[17]  Otto Muzik,et al.  A simplified analysis of [18F]3′-deoxy-3′-fluorothymidine metabolism and retention , 2005, European Journal of Nuclear Medicine and Molecular Imaging.

[18]  Stefan Eberl,et al.  Evaluation of two population-based input functions for quantitative neurological FDG PET studies , 1997, European Journal of Nuclear Medicine.

[19]  Martin A. Lodge,et al.  Non-invasive assessment of skeletal kinetics using fluorine-18 fluoride positron emission tomography: evaluation of image and population-derived arterial input functions , 1999, European Journal of Nuclear Medicine.

[20]  Mark Muzi,et al.  Kinetic modeling of 3'-deoxy-3'-fluorothymidine in somatic tumors: mathematical studies. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[21]  Klaus Wienhard,et al.  Glioma Proliferation as Assessed by 3‘-Fluoro-3’-Deoxy-l-Thymidine Positron Emission Tomography in Patients with Newly Diagnosed High-Grade Glioma , 2008, Clinical Cancer Research.

[22]  S. Shousha,et al.  Quantification of cellular proliferation in tumor and normal tissues of patients with breast cancer by [18F]fluorothymidine-positron emission tomography imaging: evaluation of analytical methods. , 2005, Cancer research.

[23]  E. Hoffman,et al.  Use of the abdominal aorta for arterial input function determination in hepatic and renal PET studies. , 1992, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[24]  G Brix,et al.  Noninvasive determination of the arterial input function of an anticancer drug from dynamic PET scans using the population approach. , 1999, Medical physics.

[25]  El Mostafa Fadaili,et al.  Comparison of Eight Methods for the Estimation of the Image-Derived Input Function in Dynamic [18F]-FDG PET Human Brain Studies , 2009, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[26]  Torsten Mattfeldt,et al.  Imaging proliferation in lung tumors with PET: 18F-FLT versus 18F-FDG. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[27]  Thomas F. Coleman,et al.  An Interior Trust Region Approach for Nonlinear Minimization Subject to Bounds , 1993, SIAM J. Optim..