Rizzo-Padoin Nathalie, Chaussard Michael, Vignal Nicolas, Kotula Ewa, Tsoupko-Sitnikov Vadim, Vaz Sofia, Hontonnou Fortune, Liu Wang-Qing, Poyet Jean-Luc, Vidal Michel, Merlet Pascal, Hosten Benoit, Sarda-Mantel Laure
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.
Assistance Publique - Hôpitaux de Paris, Hôpital Saint-Louis, Unité Claude Kellershohn, Paris, 75010, France.
Nucl Med Biol. 2016 Dec;43(12):773-780. doi: 10.1016/j.nucmedbio.2016.08.010. Epub 2016 Aug 24.
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 [F]MEL050, using for the first time, the AllInOne™ synthesis module (Trasis), and to evaluate the potential of [F]MEL050 for the detection of pigmented melanoma in mice primary subcutaneous tumors and pulmonary metastases, and to compare it with that of [F]FDG.
Automated radiosynthesis of [F]MEL050, including HPLC purification and formulation, were performed on an AllInOne™ synthesis module. [F]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 [F]MEL050 Injected Dose per g of lung tissue (%ID/g Max) was determined on PET images, compared to [F]FDG and correlated to in vivo bioluminescence imaging.
The automated radiosynthesis of [F]MEL050 required an overall radiosynthesis time of 48min, with a yield of 13-18% (not-decay corrected) and radiochemical purity higher than 99%. [F]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 [F]MEL050 and [F]FDG in subcutaneous tumors and higher TBR with [F]MEL050 than with [F]FDG in pulmonary metastases.
We successfully implemented the radiosynthesis of [F]MEL050 using the AllInOne™ module, including HPLC purification and formulation. In vivo PET/CT validation of [F]MEL050 was obtained in mouse models of pigmented melanoma, where higher [F]MEL050 uptake was observed in sub-millimetric pulmonary metastases, comparatively to [F]FDG.
黑色素瘤是一种由产生黑色素的细胞构成的高度恶性皮肤肿瘤。MEL050是一种合成的苯甲酰胺衍生分子，它能以高亲和力特异性结合黑色素。我们的目标是首次使用AllInOne™合成模块（Trasis）实现[F]MEL050的全自动放射性合成，并评估[F]MEL050在检测小鼠原发性皮下肿瘤和肺转移灶中色素性黑色素瘤方面的潜力，并将其与[F]FDG的潜力进行比较。
在AllInOne™合成模块上进行[F]MEL050的自动放射性合成，包括高效液相色谱纯化和制剂配制。[F]MEL050采用一步溴氟亲核杂环取代法合成。通过在NMRI小鼠皮下（原发性肿瘤）或静脉内（肺转移）注射B16-F10-luc2细胞诱导黑色素瘤模型。在PET图像上测定每克肺组织中[F]MEL050注射剂量的最大百分比（%ID/g Max），与[F]FDG进行比较，并与体内生物发光成像相关联。
[F]MEL050的自动放射性合成所需的总放射性合成时间为48分钟，产率为13 - 18%（未衰变校正），放射化学纯度高于99%。[F]MEL050 PET/CT图像与生物发光成像一致，显示在小鼠所有原发性皮下肿瘤和肺转移灶中放射性示踪剂摄取增加。对肿瘤和肌肉中放射性示踪剂摄取的PET定量分析表明，在皮下肿瘤中，[F]MEL050和[F]FDG的肿瘤与背景比值（TBR）相似，而在肺转移灶中，[F]MEL050的TBR高于[F]FDG。
我们成功地使用AllInOne™模块实现了[F]MEL050的放射性合成，包括高效液相色谱纯化和制剂配制。在色素性黑色素瘤小鼠模型中获得了[F]MEL050的体内PET/CT验证，其中在亚毫米级肺转移灶中观察到[F]MEL050的摄取高于[F]FDG。
