Imagerie Moléculaire et Thérapie Vectorisée, Clermont Université, Université d'Auvergne, BP 10448, 63000 Clermont-Ferrand, France,
Eur J Nucl Med Mol Imaging. 2012 Sep;39(9):1449-61. doi: 10.1007/s00259-012-2168-y. Epub 2012 Jun 16.
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.
[(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).
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.
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.
在这里，我们报告了一种新的、快速的 [(18)F]N-[2-(二乙氨基)乙基]-6-氟吡啶-3-甲酰胺 ([(18)F]ICF01006) 的放射性合成方法，该分子对黑色素组织具有高度特异性，并将其用于早期特异性检测黑色素瘤原发和播散性的小鼠模型中。
采用新的一步溴代-氟代亲核杂芳取代法合成 [(18)F]ICF01006。通过皮下（原发性肿瘤）或静脉（肺 colonies）注射 B16BL6 黑色素瘤细胞在 C57BL/6J 小鼠中诱导黑色素瘤模型。评估 [(18)F]ICF01006 正电子发射断层扫描（PET）成像在肿瘤生长的不同阶段的相关性和灵敏度，并与 [(18)F]氟脱氧葡萄糖 ([(18)F]FDG) 进行比较。
全自动 [(18)F]ICF01006 放射性合成得到 61%的放射化学产率和>99%的放射化学纯度（比活度 70-80GBq/μmol；总合成时间 42 分钟）。早在注射后 1 小时即可通过 [(18)F]ICF01006 检测到肿瘤，肿瘤摄取率分别为 1.64±0.57%、3.40±1.47%和 11.44±2.67%每克组织的注入剂量（%ID/g），分别在第 3、5 和 14 天。[(18)F]ICF01006 PET 成像还可以从肿瘤细胞接种后第 9 天开始检测黑色素瘤肺 colonies，肺放射性示踪剂的积累与黑色素瘤的侵袭相关。在第 21 天，肺部的放射性摄取达到 5.23±2.08%ID/g（与对照组小鼠的 0.41±0.90%ID/g 相比）。在两种模型中，与 [(18)F]FDG 的比较表明，两种放射性示踪剂均能够检测到黑色素瘤病变，但 [(18)F]ICF01006 在对比度和特异性方面更具优势。
我们有希望的结果提供了进一步的临床前数据，进一步加强了 [(18)F]ICF01006 PET 成像在黑色素瘤阳性播散性黑色素瘤的早期特异性诊断和随访中的优异潜力。
