Early detection and longitudinal monitoring of experimental primary and disseminated melanoma using [¹⁰F]ICF01006, a highly promising melanoma PET tracer.
OBJECTIVE
Here, we report a new and rapid radiosynthesis of (18)F-N-[2-(diethylamino)ethyl]-6-fluoro-pyridine-3-carboxamide ([(18)F]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
[(18)F]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 [(18)F]ICF01006 were evaluated at different stages of tumoural growth and compared to (18)F-fluorodeoxyglucose ([(18)F]FDG).


RESULTS
The fully automated radiosynthesis of [(18)F]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 [(18)F]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. [(18)F]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 [(18)F]FDG showed that both radiotracers were able to detect melanoma lesions, but [(18)F]ICF01006 was superior in terms of contrast and specificity.


CONCLUSIONS
Our promising results provide further preclinical data, reinforcing the excellent potential of [(18)F]ICF01006 PET imaging for early specific diagnosis and follow-up of melanin-positive disseminated melanoma.
Imagerie Moléculaire et Thérapie Vectorisée, Clermont Université, Université d'Auvergne, BP 10448, 63000 Clermont-Ferrand, France, latifa.rbah@inserm.fr
Latifa
L
Rbah-Vidal
Aurélien
A
Vidal
Sophie
S
Besse
Florent
F
Cachin
Mathilde
M
Bonnet
Laurent
L
Audin
Serge
S
Askienazy
Frédéric
F
Dollé
Françoise
F
Degoul
Elisabeth
E
Miot-Noirault
Nicole
N
Moins
Philippe
P
Auzeloux
Jean-Michel
JM
Chezal
D000818:Animals; D001692:Biological Transport; D055088:Early Detection of Cancer / Q000379:methods*; D008137:Longitudinal Studies; D008297:Male; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011849:Radioactive Tracers; D011854:Radiochemistry
C543821:N-(2-(diethylamino)ethyl)-6-fluoronicotinamide; D011849:Radioactive Tracers; D009536:Niacinamide