[18F]MEL050 as a melanin-targeted PET tracer: Fully automated radiosynthesis and comparison to18F-FDG for the detection of pigmented melanoma in mice primary subcutaneous tumors and pulmonary metastases.
BACKGROUND
Melanoma is a highly malignant cutaneous tumor of melanin-producing cells. MEL050 is a synthetic benzamide-derived molecule that specifically binds to melanin with high affinity. Our aim was to implement a fully automated radiosynthesis of [18F]MEL050, using for the first time, the AllInOne™ synthesis module (Trasis), and to evaluate the potential of [18F]MEL050 for the detection of pigmented melanoma in mice primary subcutaneous tumors and pulmonary metastases, and to compare it with that of [18F]FDG.


METHODS
Automated radiosynthesis of [18F]MEL050, including HPLC purification and formulation, were performed on an AllInOne™ synthesis module. [18F]MEL050 was synthesized using a one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumor) or intravenous (pulmonary metastases) injection of B16-F10-luc2 cells in NMRI mice. The maximum percentage of [18F]MEL050 Injected Dose per g of lung tissue (%ID/g Max) was determined on PET images, compared to [18F]FDG and correlated to in vivo bioluminescence imaging.


RESULTS
The automated radiosynthesis of [18F]MEL050 required an overall radiosynthesis time of 48min, with a yield of 13-18% (not-decay corrected) and radiochemical purity higher than 99%. [18F]MEL050 PET/CT images were concordant with bioluminescence imaging, showing increased radiotracer uptake in all primary subcutaneous tumors and pulmonary metastases of mice. PET quantification of radiotracers uptake in tumors and muscles demonstrated similar tumor-to-background ratio (TBR) with [18F]MEL050 and [18F]FDG in subcutaneous tumors and higher TBR with [18F]MEL050 than with [18F]FDG in pulmonary metastases.


CONCLUSIONS
We successfully implemented the radiosynthesis of [18F]MEL050 using the AllInOne™ module, including HPLC purification and formulation. In vivo PET/CT validation of [18F]MEL050 was obtained in mouse models of pigmented melanoma, where higher [18F]MEL050 uptake was observed in sub-millimetric pulmonary metastases, comparatively to [18F]FDG.
Assistance Publique - Hôpitaux de Paris, Hôpital Saint-Louis, Unité Claude Kellershohn, Paris, 75010, France; Inserm, UMR-S 1144, Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, 75006, France. Electronic address: nathalie.rizzo@aphp.fr.
Nathalie
N
Rizzo-Padoin
Assistance Publique - Hôpitaux de Paris, Hôpital Saint-Louis, Unité Claude Kellershohn, Paris, 75010, France.
Michael
M
Chaussard
Assistance Publique - Hôpitaux de Paris, Hôpital Saint-Louis, Unité Claude Kellershohn, Paris, 75010, France; Inserm, UMR-S 1144, Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, 75006, France.
Nicolas
N
Vignal
Inserm, UMRS 1160, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, 75010, France.
Ewa
E
Kotula
Assistance Publique - Hôpitaux de Paris, Hôpital Saint-Louis, Unité Claude Kellershohn, Paris, 75010, France.
Vadim
V
Tsoupko-Sitnikov
Assistance Publique - Hôpitaux de Paris, Hôpital Lariboisière, Médecine nucléaire, Paris, 75010, France.
Sofia
S
Vaz
Assistance Publique - Hôpitaux de Paris, Hôpital Saint-Louis, Unité Claude Kellershohn, Paris, 75010, France; Université Paris Diderot, Paris, 75010, France.
Fortune
F
Hontonnou
UMR 8638 CNRS, Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, 75006, France.
Wang-Qing
WQ
Liu
Inserm, UMRS 1160, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, 75010, France; Université Paris Diderot, Paris, 75010, France.
Jean-Luc
JL
Poyet
UMR 8638 CNRS, Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, 75006, France.
Michel
M
Vidal
Université Paris Diderot, Paris, 75010, France; Assistance Publique - Hôpitaux de Paris, Hôpital Saint-Louis, Médecine nucléaire, Paris, 75010, France.
Pascal
P
Merlet
Assistance Publique - Hôpitaux de Paris, Hôpital Saint-Louis, Unité Claude Kellershohn, Paris, 75010, France; Inserm, UMR-S 1144, Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, 75006, France.
Benoit
B
Hosten
Assistance Publique - Hôpitaux de Paris, Hôpital Saint-Louis, Unité Claude Kellershohn, Paris, 75010, France; Assistance Publique - Hôpitaux de Paris, Hôpital Lariboisière, Médecine nucléaire, Paris, 75010, France; Université Paris Diderot, Paris, 75010, France; Inserm UMR-S 942, Hôpital Lariboisière, Paris, 75010, France.
Laure
L
Sarda-Mantel
D000818:Animals; D001331:Automation; D045744:Cell Line, Tumor; D019788:Fluorodeoxyglucose F18; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary; D008543:Melanins / Q000378:metabolism*; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D010858:Pigmentation; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D011854:Radiochemistry / Q000379:methods*
D008543:Melanins; C543821:N-(2-(diethylamino)ethyl)-6-fluoronicotinamide; D019788:Fluorodeoxyglucose F18; D009536:Niacinamide
Melanin; Melanoma; PET imaging; Radiosynthesis; Small-animal PET; [(18)F]MEL050