Centre for Cancer Imaging and Translational Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
J Nucl Med. 2011 Jan;52(1):115-22. doi: 10.2967/jnumed.110.078154. Epub 2010 Dec 13.
The efficacy of differing routes of administration of 18F-6-fluoro-N-[2-(diethylamino)ethyl] pyridine-3-carboxamide (18F-MEL050), a new benzamide-based PET radiotracer for imaging regional lymph node metastasis in melanoma, was assessed.
B16-Black/6 metastatic melanoma cells harboring an mCherry transgene were implanted into the left-upper-foot surface of 49 C57 Black/6 mice as a model of popliteal lymph node (PLN) metastasis. Ultrasound scanning of the left PLN was performed at baseline and in combination with 18F-MEL050 PET on days 5, 9, and 14. Mice were divided into 2 groups to compare the results of tracer administration either subcutaneously at the tumor site (local) or in the lateral tail vein (systemic). After PET on each imaging day, 5 mice per group-including any with evidence of metastasis-were sacrificed for ex vivo validation studies including assessment of retained radioactivity and presence of the mCherry transgene as a surrogate of nodal tumor burden.
Nine mice were judged as positive for PLN metastasis by ultrasound at day 5, and 8 PLNs were positive on 18F-MEL050 PET, 3 after systemic and 5 after local administration. Ex vivo analysis showed that ultrasound correctly identified 90% of positive PLNs, with 1 false-positive. 18F-MEL050 PET correctly identified 60% of positive PLNs after systemic administration and 100% after local administration with no false-positive results by either route. The average node-to-background ratio for positive PLNs was 6.8 in the systemic-administration group and correlated with disease burden. In the local-administration group, the mean uptake ratio was 48, without clear relation to metastatic burden. Additional sites of metastatic disease were also correctly identified by 18F-MEL050 PET.
In addition to its potential for systemic staging, perilesional administration of 18F-MEL050 may allow sensitive and specific, noninvasive identification of regional lymph node metastasis in pigmented malignant melanomas.
评估新型苯甲酰胺类 PET 示踪剂 18F-6-氟-N-[2-(二乙氨基)乙基]吡啶-3-甲酰胺（18F-MEL050）不同给药途径对黑色素瘤局部淋巴结转移成像的疗效。
将携带 mCherry 转基因的 B16-Black/6 黑色素瘤细胞植入 49 只 C57Black/6 小鼠左前足表面，建立隐窝淋巴结（PLN）转移模型。在基线和第 5、9 和 14 天，用超声扫描左 PLN，结合 18F-MEL050 PET。将小鼠分为 2 组，比较在肿瘤部位（局部）或尾静脉（系统）皮下给药的结果。在每个成像日进行 PET 后，每组 5 只小鼠（包括任何有转移证据的小鼠）被处死，进行离体验证研究，包括评估放射性保留和 mCherry 转基因的存在，作为淋巴结肿瘤负荷的替代物。
9 只小鼠在第 5 天通过超声判断为 PLN 转移阳性，8 只 PLN 在 18F-MEL050 PET 上呈阳性，3 只经系统给药，5 只经局部给药。离体分析显示，超声正确识别了 90%的阳性 PLN，有 1 个假阳性。全身给药后，18F-MEL050 PET 正确识别了 60%的阳性 PLN，而局部给药则为 100%，两种途径均无假阳性结果。阳性 PLN 的平均淋巴结与背景比值在全身给药组为 6.8，与疾病负担相关。在局部给药组，平均摄取比值为 48，与转移负担无明显关系。18F-MEL050 PET 还可正确识别其他转移部位。
除了全身分期的潜力外，18F-MEL050 瘤周给药可能允许敏感和特异性、非侵入性地识别黑色素瘤的局部淋巴结转移。
