Delving into the Latest Updates on 18F-MEL050 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug, Diagnostic radiopharmaceuticals

Synonyms

[18F]ICF-01006, [18F]MEL-050

Target

Melanin

Action

inhibitors, enhancers

Mechanism

Melanin inhibitors, PET imaging(Positron-emission tomography enhancers)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication-

Inactive Indication

Melanoma

Originator Organization-

Active Organization-

Inactive Organization

Institut National de la Santé et de la Recherche Médicale

License Organization-

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC12H18FN3O

InChIKeyKDJDPOPMAGYJLH-HSGWXFLFSA-N

CAS Registry1186533-83-4

The rapid synthesis of two radiofluoronicotinamide derivatives, namely, [¹⁸F]MEL050 and [¹⁸F]MEL-2F has been simply performed starting from commercial materials. [¹⁸F]MEL-2F is a new, potential analogue PET-probe for melanoma imaging. [¹⁸F]MEL050 is already an excellent PET imaging probe for early specific diagnosis. The synthesis involves coupling step to obtain the precursor followed by radiofluorination. During the synthesis of the precursors different coupling reagents, such as HBTU, TFFH, HOBT, COMU and PyCIU have been applied. PyClU was found the best to reduce the coupling period to < 1h. The labeled compounds were isolated and purified by HPLC. In the in-vitro study three kinds of cells, namely, Melur (melanin free), KB-3 carcinoma cell line (non-melanoma) and B16-F10 melanoma cell line were used to evaluate the uptake of the radiotracers.

01 Sep 2017·Nuclear medicine and biologyQ4 · MEDICINE

Dose-on-demand production of diverse 18 F-radiotracers for preclinical applications using a continuous flow microfluidic system

Q4 · MEDICINE

Article

Author: Greguric, Ivan ; Pascali, Giancarlo ; Matesic, Lidia ; Kallinen, Annukka

INTRODUCTION:

The production of ¹⁸F-radiotracers using continuous flow microfluidics is under-utilized due to perceived equipment limitations. We describe the dose-on-demand principle, whereby the back-to-back production of multiple, diverse ¹⁸F-radiotracers can be prepared on the same day, on the same microfluidic system using the same batch of [¹⁸F]fluoride, the same microreactor, the same HPLC column and SPE cartridge to obtain a useful production yield.

METHODS:

[¹⁸F]MEL050, [¹⁸F]Fallypride and [¹⁸F]PBR111 were radiolabeled with [¹⁸F]fluoride using the Advion NanoTek Microfluidic Synthesis System. The outlet of the microreactor was connected to an automated HPLC injector and following the collection of the product, SPE reformulation produced the ¹⁸F-radiotracer in <10% ethanolic saline. A thorough automated cleaning procedure was implemented to ensure no cross-contamination between radiotracer synthesis.

RESULTS:

The complete productions for [¹⁸F]MEL050 and [¹⁸F]Fallypride were performed at total flow rates of 20μL/min, resulting in 40±13% and 25±13% RCY respectively. [¹⁸F]PBR111 was performed at 200μL/min to obtain 27±8% RCY. Molar activities for each ¹⁸F-radiotracer were >100GBq/μmol and radiochemical purities were >97%, implying that the cleaning procedure was effective.

CONCLUSIONS:

Using the same initial solution of [¹⁸F]fluoride, microreactor, HPLC column and SPE cartridge, three diverse ¹⁸F-radiotracers could be produced in yields sufficient for preclinical studies in a back-to-back fashion using a microfluidic system with no detectable cross-contamination.

01 Dec 2016·Nuclear medicine and biologyQ4 · MEDICINE

[ 18 F]MEL050 as a melanin-targeted PET tracer: Fully automated radiosynthesis and comparison to 18 F-FDG for the detection of pigmented melanoma in mice primary subcutaneous tumors and pulmonary metastases

Q4 · MEDICINE

Article

Author: Chaussard, Michael ; Vidal, Michel ; Kotula, Ewa ; Rizzo-Padoin, Nathalie ; Sarda-Mantel, Laure ; Hosten, Benoit ; Poyet, Jean-Luc ; Hontonnou, Fortune ; Vaz, Sofia ; Merlet, Pascal ; Liu, Wang-Qing ; Tsoupko-Sitnikov, Vadim ; Vignal, Nicolas

INTRODUCTION:

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.

CONCLUSION:

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.

100 Deals associated with 18F-MEL050

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