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Research ArticleOncology

Effect of Carbidopa on 18F-FDOPA Uptake in Insulinoma: From Cell Culture to Small-Animal PET Imaging

Julien Detour, Alice Pierre, Fréderic Boisson, Guillaume Kreutter, Thomas Lavaux, Izzie Jacques Namer, Laurence Kessler, David Brasse, Patrice Marchand and Alessio Imperiale
Journal of Nuclear Medicine January 2017, 58 (1) 36-41; DOI: https://doi.org/10.2967/jnumed.116.180588
Julien Detour
1Department of Radiopharmacy, Strasbourg University Hospitals, Strasbourg, France
2Department of Biophysics and Nuclear Medicine, Strasbourg University Hospitals, Strasbourg, France
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Alice Pierre
1Department of Radiopharmacy, Strasbourg University Hospitals, Strasbourg, France
2Department of Biophysics and Nuclear Medicine, Strasbourg University Hospitals, Strasbourg, France
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Fréderic Boisson
3Institut Pluridisciplinaire Hubert Curien (IPHC), CNRS/UMR7178, Strasbourg University, Strasbourg, France
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Guillaume Kreutter
4EA7293, Vascular and Tissular Stress in Transplantation, Illkirch, France
5Federation of Translational Medicine of Strasbourg (FMTS), Faculty of Medicine, Strasbourg University, Strasbourg, France
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Thomas Lavaux
6Department of Biochemistry and Molecular Biology, Strasbourg University Hospitals, Strasbourg, France
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Izzie Jacques Namer
2Department of Biophysics and Nuclear Medicine, Strasbourg University Hospitals, Strasbourg, France
5Federation of Translational Medicine of Strasbourg (FMTS), Faculty of Medicine, Strasbourg University, Strasbourg, France
7ICube, CNRS/UMR7357, Strasbourg University, Strasbourg, France; and
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Laurence Kessler
4EA7293, Vascular and Tissular Stress in Transplantation, Illkirch, France
5Federation of Translational Medicine of Strasbourg (FMTS), Faculty of Medicine, Strasbourg University, Strasbourg, France
8Department of Diabetology, Strasbourg University Hospitals, Strasbourg, France
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David Brasse
3Institut Pluridisciplinaire Hubert Curien (IPHC), CNRS/UMR7178, Strasbourg University, Strasbourg, France
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Patrice Marchand
3Institut Pluridisciplinaire Hubert Curien (IPHC), CNRS/UMR7178, Strasbourg University, Strasbourg, France
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Alessio Imperiale
2Department of Biophysics and Nuclear Medicine, Strasbourg University Hospitals, Strasbourg, France
3Institut Pluridisciplinaire Hubert Curien (IPHC), CNRS/UMR7178, Strasbourg University, Strasbourg, France
5Federation of Translational Medicine of Strasbourg (FMTS), Faculty of Medicine, Strasbourg University, Strasbourg, France
7ICube, CNRS/UMR7357, Strasbourg University, Strasbourg, France; and
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  • FIGURE 1.
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    FIGURE 1.

    Accumulation of 18F-FDOPA in RIN-5mF cells. Tracer accumulation was measured in classical RPMI culture medium and amino acid–free medium (PBS-Glu medium). Values represent mean percentage of uptake for 106 cells ± SE of mean. (A) Effect of carbidopa (80 μM) on 18F-FDOPA uptake in RPMI culture medium (n = 12 for each condition) and in PBS-Glu medium (n = 4 for each condition). *P < 0.05 (Mann–Whitney U test). (B) Effect of BCH (10 mM; n = 4) and tetrabenazine (TBZ; 10 μM; n = 2) on 18F-FDOPA uptake in RPMI culture medium. #P < 0.05 (Mann–Whitney U test).

  • FIGURE 2.
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    FIGURE 2.

    Functional and pathologic characterization of insulinoma xenografts. (A) Morning serum glycemia levels in blood samples collected from 10 nonfasting mice with xenografts. Dashed line represents introduction of 20% glucose solution instead of water. (B) Insulinoma xenograft of 1.4 × 1.3 mm (arrow) developed 15 d after subcutaneous injection of 6 × 106 RIN-5mF cells. Insulinoma-bearing mice died after hypoglycemic crisis (serum glycemia, 18 mg/dL). (C) Histologic analysis of RIN-5mF xenograft tumor showing epithelioid and spindle cells (hematoxylin–eosin stain, ×400). (D) Immunohistochemical analysis of RIN-5mF xenograft tumor showing insulin-positive immunostaining.

  • FIGURE 3.
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    FIGURE 3.

    Representative anterior view of 18F-FDOPA PET maximum-intensity-projection images obtained without (A) and with (B) carbidopa (CD) premedication of 2 nude mice with subcutaneous insulinoma xenografts of 38 and 52 mm3, respectively, in right hind legs (arrows). Images were reconstructed from summed time frames of 0–5 min (early phase) and 15–20 min (delayed phase) after intravenous 18F-FDOPA injection. Insulinomas were detected regardless of carbidopa treatment. Moreover, tumor SUV in treated mice was higher than that in nontreated mice for both early and delayed PET acquisitions (SUVs: no CD, early phase, 0.94; no CD, delayed phase, 0.46; CD, early phase, 1.46; CD, delayed phase, 1.03).

  • FIGURE 4.
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    FIGURE 4.

    18F-FDOPA PET time–activity curves for insulinoma xenografts according to carbidopa (CD) premedication (no CD vs. CD). Tumors from CD-treated mice showed significantly higher 18F-FDOPA uptake over whole PET acquisition than tumors from nontreated mice (P < 0.05). SUVs are reported as median and interquartile range.

  • FIGURE 5.
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    FIGURE 5.

    Biodistribution of 18F-FDOPA in mice bearing insulinoma xenografts according to carbidopa (CD) premedication (no CD vs. CD). SUVs (mean ± SE of mean) were obtained from summed time frames of 0–5 min (early phase) and 15–20 min (delayed phase) in dynamic PET study after 18F-FDOPA injection. 18F-FDOPA degradation in peripheral organs was inhibited by CD, with consequent increase in radiotracer availability and accumulation in abdominal organs. Statistical significance was not reached, probably because of small number of animals analyzed.

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Journal of Nuclear Medicine: 58 (1)
Journal of Nuclear Medicine
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January 1, 2017
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Effect of Carbidopa on 18F-FDOPA Uptake in Insulinoma: From Cell Culture to Small-Animal PET Imaging
Julien Detour, Alice Pierre, Fréderic Boisson, Guillaume Kreutter, Thomas Lavaux, Izzie Jacques Namer, Laurence Kessler, David Brasse, Patrice Marchand, Alessio Imperiale
Journal of Nuclear Medicine Jan 2017, 58 (1) 36-41; DOI: 10.2967/jnumed.116.180588

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Effect of Carbidopa on 18F-FDOPA Uptake in Insulinoma: From Cell Culture to Small-Animal PET Imaging
Julien Detour, Alice Pierre, Fréderic Boisson, Guillaume Kreutter, Thomas Lavaux, Izzie Jacques Namer, Laurence Kessler, David Brasse, Patrice Marchand, Alessio Imperiale
Journal of Nuclear Medicine Jan 2017, 58 (1) 36-41; DOI: 10.2967/jnumed.116.180588
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Keywords

  • 18F-FDOPA
  • PET
  • insulinoma
  • carbidopa
  • small-animal PET
  • RIN-m5F
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