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Research ArticleOncology

Assessment of Tryptophan Uptake and Kinetics Using 1-(2-18F-Fluoroethyl)-l-Tryptophan and α-11C-Methyl-l-Tryptophan PET Imaging in Mice Implanted with Patient-Derived Brain Tumor Xenografts

Sharon K. Michelhaugh, Otto Muzik, Anthony R. Guastella, Neil V. Klinger, Lisa A. Polin, Hancheng Cai, Yangchun Xin, Thomas J. Mangner, Shaohui Zhang, Csaba Juhász and Sandeep Mittal
Journal of Nuclear Medicine February 2017, 58 (2) 208-213; DOI: https://doi.org/10.2967/jnumed.116.179994
Sharon K. Michelhaugh
1Department of Neurosurgery, Wayne State University, Detroit, Michigan
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Otto Muzik
2Department of Pediatrics, Wayne State University, Detroit, Michigan
3Department of Radiology, Wayne State University, Detroit, Michigan
4PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, Michigan
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Anthony R. Guastella
1Department of Neurosurgery, Wayne State University, Detroit, Michigan
5Department of Oncology, Wayne State University, Detroit, Michigan
6Karmanos Cancer Institute, Detroit, Michigan
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Neil V. Klinger
1Department of Neurosurgery, Wayne State University, Detroit, Michigan
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Lisa A. Polin
5Department of Oncology, Wayne State University, Detroit, Michigan
6Karmanos Cancer Institute, Detroit, Michigan
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Hancheng Cai
7Department of Radiology and Advanced Imaging Research Center, University of Texas Southwestern, Dallas, Texasand
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Yangchun Xin
7Department of Radiology and Advanced Imaging Research Center, University of Texas Southwestern, Dallas, Texasand
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Thomas J. Mangner
3Department of Radiology, Wayne State University, Detroit, Michigan
4PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, Michigan
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Shaohui Zhang
4PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, Michigan
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Csaba Juhász
2Department of Pediatrics, Wayne State University, Detroit, Michigan
4PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, Michigan
6Karmanos Cancer Institute, Detroit, Michigan
8Department of Neurology, Wayne State University, Detroit, Michigan
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Sandeep Mittal
1Department of Neurosurgery, Wayne State University, Detroit, Michigan
5Department of Oncology, Wayne State University, Detroit, Michigan
6Karmanos Cancer Institute, Detroit, Michigan
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  • FIGURE 1.
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    FIGURE 1.

    KP of tryptophan metabolism. (A) Abridged KP overview. Enzymes in blue represent rate-limiting step. (B and C) Structures of 18F-FETrp and 11C-AMT, respectively.

  • FIGURE 2.
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    FIGURE 2.

    Biodistribution of 18F-FETrp and 11C-AMT between 30 and 60 min. Two coronal slices of 14-038 glioblastoma PDX mouse showing pancreas, gallbladder, and bladder in one plane with kidneys in other. Color scale bar represents SUV range for both tracers. (A) For 18F-FETrp, high uptake is observed in both bladder and pancreas, with lesser uptake in gallbladder. Minimal uptake is seen in kidneys. (B) For 11C-AMT, tracer uptake is high in bladder and kidneys, with low uptake detected in pancreas and gallbladder.

  • FIGURE 3.
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    FIGURE 3.

    Time-dependent SUV curves characterizing 18F-FETrp and 11C-AMT tracers. Averaged SUVs for indicated organs (n = 5). Error bars represent SD. (A) 11C-AMT tracer uptake is initially high in kidneys and undergoes washout to bladder, where activity increases with time. (B) 18F-FETrp tracer shows increasing uptake in bladder, followed by relatively constant retention in pancreas and intestines. For both tracers, brain displays slow but steady accumulation.

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    FIGURE 4.

    Comparison of tumoral tracer uptake between 18F-FETrp and 11C-AMT in the 14-038 glioblastoma PDX mouse. Mouse was injected with 18F-FETrp, followed by 11C-AMT 7 d later. (A) 18F-FETrp tracer (left) and 11C-AMT tracer (right). 18F-FETrp shows increased tumoral tracer accumulation compared with 11C-AMT. Color scale bar represents SUV range for both tracers. (B) Corresponding time–activity curves confirm higher tracer retention for 18F-FETrp.

  • FIGURE 5.
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    FIGURE 5.

    Comparison of 11C-AMT and 18F-FETrp PET SUVs for PDX tumors. (A) In glioblastoma, breast metastatic tumors, and non–small cell lung cancer metastatic tumors, 18F-FETrp SUVs were greater than 11C-AMT SUVs. (B) 18F-FETrp SUVs were significantly greater than 11C-AMT SUVs (paired t test).

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    TABLE 1

    Xenograft-Bearing Mouse Characteristics

    Tumor IDTumor typeMouse passage #Days between scansRight tumor (mg)*Left tumor (mg)*18F-FETrp dose (MBq/g)11C-AMT dose (MBq/g)
    14-038Glioblastoma773441720.361.15
    14-112SNSCLC met533512560.451.32
    15-015Breast cancer met573201960.261.24
    15-017Breast cancer met8*3002210.28†
    15-037Glioblastoma713202210.401.19
    15-070Breast cancer met342883040.381.30
    • ↵* Tumor measurements ∼2 d of 18F-FETrp scans.

    • ↵† 18F-FETrp imaging only.

    • NSCLC = non–small cell lung cancer; met = metastasis.

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    TABLE 2

    Radiation Absorbed Dose from 18F-FETrp PET Studies in Adult Control Subjects

    SubjectEffective dose (μSv/MBq [rem/mCi])Critical organ, pancreas (μSv/MBq [rad/mCi])Effective PET dose (mSv [rem])
    Control male (70 kg)20.9 (0.077)151 (0.557)7.3 (0.756)
    Control female (57 kg)23.2 (0.086)168 (0.621)8.1 (0.843)
    • For injected activity of 5 MBq/kg (0.14 mCi/kg).

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Journal of Nuclear Medicine: 58 (2)
Journal of Nuclear Medicine
Vol. 58, Issue 2
February 1, 2017
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Assessment of Tryptophan Uptake and Kinetics Using 1-(2-18F-Fluoroethyl)-l-Tryptophan and α-11C-Methyl-l-Tryptophan PET Imaging in Mice Implanted with Patient-Derived Brain Tumor Xenografts
Sharon K. Michelhaugh, Otto Muzik, Anthony R. Guastella, Neil V. Klinger, Lisa A. Polin, Hancheng Cai, Yangchun Xin, Thomas J. Mangner, Shaohui Zhang, Csaba Juhász, Sandeep Mittal
Journal of Nuclear Medicine Feb 2017, 58 (2) 208-213; DOI: 10.2967/jnumed.116.179994

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Assessment of Tryptophan Uptake and Kinetics Using 1-(2-18F-Fluoroethyl)-l-Tryptophan and α-11C-Methyl-l-Tryptophan PET Imaging in Mice Implanted with Patient-Derived Brain Tumor Xenografts
Sharon K. Michelhaugh, Otto Muzik, Anthony R. Guastella, Neil V. Klinger, Lisa A. Polin, Hancheng Cai, Yangchun Xin, Thomas J. Mangner, Shaohui Zhang, Csaba Juhász, Sandeep Mittal
Journal of Nuclear Medicine Feb 2017, 58 (2) 208-213; DOI: 10.2967/jnumed.116.179994
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