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Early detection and longitudinal monitoring of experimental primary and disseminated melanoma using [18F]ICF01006, a highly promising melanoma PET tracer

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Here, we report a new and rapid radiosynthesis of 18F-N-[2-(diethylamino)ethyl]-6-fluoro-pyridine-3-carboxamide ([18F]ICF01006), a molecule with a high specificity for melanotic tissue, and its evaluation in a murine model for early specific detection of pigmented primary and disseminated melanoma.

Methods

[18F]ICF01006 was synthesized using a new one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumour) or intravenous (lung colonies) injection of B16BL6 melanoma cells in C57BL/6J mice. The relevance and sensitivity of positron emission tomography (PET) imaging using [18F]ICF01006 were evaluated at different stages of tumoural growth and compared to 18F-fluorodeoxyglucose ([18F]FDG).

Results

The fully automated radiosynthesis of [18F]ICF01006 led to a radiochemical yield of 61 % and a radiochemical purity >99 % (specific activity 70–80 GBq/μmol; total synthesis time 42 min). Tumours were visualized before they were palpable as early as 1 h post-injection with [18F]ICF01006 tumoural uptake of 1.64 ± 0.57, 3.40 ± 1.47 and 11.44 ± 2.67 percentage of injected dose per gram of tissue (%ID/g) at days 3, 5 and 14, respectively. [18F]ICF01006 PET imaging also allowed detection of melanoma pulmonary colonies from day 9 after tumour cell inoculation, with a lung radiotracer accumulation correlated with melanoma invasion. At day 21, radioactivity uptake in lungs reached a value of 5.23 ± 2.08 %ID/g (versus 0.41 ± 0.90 %ID/g in control mice). In the two models, comparison with [18F]FDG showed that both radiotracers were able to detect melanoma lesions, but [18F]ICF01006 was superior in terms of contrast and specificity.

Conclusion

Our promising results provide further preclinical data, reinforcing the excellent potential of [18F]ICF01006 PET imaging for early specific diagnosis and follow-up of melanin-positive disseminated melanoma.

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Acknowledgments

This research was supported by TRT/PET/MEL Program (2008-2013) of CLARA Rhône-Alpes Auvergne. The [18F]FDG tracer was kindly provided by the Cancer Center Jean Perrin of Clermont-Ferrand, France (GlucoTEP/CYCLOPHARMA Laboratories). The authors would like to acknowledge Janine Papon and Pr. Laurent Sarry for their excellent technical and scientific help.

Conflicts of interest

None.

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Authors and Affiliations

  1. Imagerie Moléculaire et Thérapie Vectorisée, Clermont Université, Université d’Auvergne, BP 10448, 63000, Clermont-Ferrand, France

    Latifa Rbah-Vidal, Aurélien Vidal, Sophie Besse, Florent Cachin, Laurent Audin, Françoise Degoul, Elisabeth Miot-Noirault, Nicole Moins, Philippe Auzeloux & Jean-Michel Chezal

  2. Inserm, U 990, 63005, Clermont-Ferrand, France

    Latifa Rbah-Vidal, Aurélien Vidal, Sophie Besse, Florent Cachin, Laurent Audin, Françoise Degoul, Elisabeth Miot-Noirault, Nicole Moins, Philippe Auzeloux & Jean-Michel Chezal

  3. Centre Jean Perrin, 63011, Clermont-Ferrand, France

    Florent Cachin

  4. CYCLOPHARMA Laboratories, Biopôle Clermont-Limagne, 63360, Saint-Beauzire, France

    Serge Askienazy

  5. U1071 INSERM-Université d’Auvergne, M2USH, 63000, Clermont-Ferrand, France

    Mathilde Bonnet

  6. CEA, I2BM, Service Hospitalier Frédéric Joliot, 91401, Orsay, France

    Frédéric Dollé

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  1. Latifa Rbah-Vidal
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  2. Aurélien Vidal
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  6. Laurent Audin
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  9. Françoise Degoul
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  10. Elisabeth Miot-Noirault
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  11. Nicole Moins
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Correspondence to Latifa Rbah-Vidal.

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Rbah-Vidal, L., Vidal, A., Besse, S. et al. Early detection and longitudinal monitoring of experimental primary and disseminated melanoma using [18F]ICF01006, a highly promising melanoma PET tracer. Eur J Nucl Med Mol Imaging 39, 1449–1461 (2012). https://doi.org/10.1007/s00259-012-2168-y

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