Early detection and longitudinal monitoring of experimental primary and disseminated melanoma using [18F]ICF01006, a highly promising melanoma PET tracer
Early detection and longitudinal monitoring of experimental primary and disseminated melanoma using [18F]ICF01006, a highly promising melanoma PET tracer
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DOI：
10.1007/s00259-012-2168-y
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发表时间：
2012-09-01
影响因子：
9.1
通讯作者：
Chezal, Jean-Michel
中科院分区：
文献类型：
--
作者：
Rbah-Vidal, Latifa;Vidal, Aurelien;Chezal, Jean-Michel
在这里，我们报告了一种新的快速放射合成的F-18-N-[2-（二乙基氨基）乙基]-6-氟-吡啶-3-甲酰胺（[F-18] ICF 01006），一种对黑色素组织具有高度特异性的分子，以及其在小鼠模型中对色素性原发性和播散性黑色素瘤早期特异性检测的评价。[F-18] ICF 01006是采用一种新的溴对氟亲核取代反应一步合成的。通过在C57 BL/6 J小鼠中皮下（原发性肿瘤）或静脉内（肺集落）注射B16 BL 6黑素瘤细胞来诱导黑素瘤模型。在肿瘤生长的不同阶段评价了使用[F-18] ICF 01006的正电子发射断层扫描（PET）成像的相关性和灵敏度，并与F-18-氟脱氧葡萄糖进行了比较[F-18] ICF 01006的全自动放射合成导致61%的放射化学产率和> 99%的放射化学纯度。（比活度70-80 GBq/μ mol;总合成时间42分钟）。早在注射后1小时，在肿瘤可触及之前对其进行可视化，在第3、5和14天，[F-18] ICF 01006肿瘤摄取分别为1.64 +/- 0.57、3.40 +/- 1.47和11.44 +/-2.67%注射剂量/克组织（%ID/g）。[F-18] ICF 01006 PET成像还允许在肿瘤细胞接种后第9天检测黑色素瘤肺集落，肺放射性示踪剂蓄积与黑色素瘤侵袭相关。在第21天，肺中的放射性摄取达到5.23 +/-2.08% ID/g的值（对照小鼠为0.41 +/-0.90% ID/g）。在这两种模型中，与[F-18]FDG的比较表明，两种放射性示踪剂都能够检测到黑色素瘤病变，但[F-18] ICF 01006在对比度和特异性方面上级。我们有希望的结果提供了进一步的临床前数据，加强了[F-18] ICF 01006 PET成像在黑色素阳性播散性黑色素瘤早期特异性诊断和随访方面的出色潜力。
Here, we report a new and rapid radiosynthesis of F-18-N-[2-(diethylamino)ethyl]-6-fluoro-pyridine-3-carboxamide ([F-18]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.[F-18]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 [F-18]ICF01006 were evaluated at different stages of tumoural growth and compared to F-18-fluorodeoxyglucose ([F-18]FDG).The fully automated radiosynthesis of [F-18]ICF01006 led to a radiochemical yield of 61 % and a radiochemical purity > 99 % (specific activity 70-80 GBq/mu mol; total synthesis time 42 min). Tumours were visualized before they were palpable as early as 1 h post-injection with [F-18]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. [F-18]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 [F-18]FDG showed that both radiotracers were able to detect melanoma lesions, but [F-18]ICF01006 was superior in terms of contrast and specificity.Our promising results provide further preclinical data, reinforcing the excellent potential of [F-18]ICF01006 PET imaging for early specific diagnosis and follow-up of melanin-positive disseminated melanoma.