Arulappu Appitha, Battle Mark, Eisenblaetter Michel, McRobbie Graeme, Khan Imtiaz, Monypenny James, Weitsman Gregory, Galazi Myria, Hoppmann Susan, Gazinska Patrycja, Wulaningsih Wulan, Dalsgaard Grethe Tang, Macholl Sven, Ng Tony
Richard Dimbleby Department of Cancer Research, Kings College London, London, United Kingdom.
GE Healthcare, Life Sciences, Amersham, United Kingdom.
J Nucl Med. 2016 May;57(5):765-70. doi: 10.2967/jnumed.115.164384. Epub 2015 Dec 3.
Locoregional recurrence of breast cancer poses significant clinical problems because of frequent inoperability once the chest wall is involved. Early detection of recurrence by molecular imaging agents against therapeutically targetable receptors, such as c-Met, would be of potential benefit. The aim of this study was to assess (18)F-AH113804, a peptide-based molecular imaging agent with high affinity for human c-Met, for the detection of early-stage locoregional recurrence in a human basal-like breast cancer model, HCC1954.
HCC1954 tumor-bearing xenograft models were established, and (18)F-AH113804 was administered. Distribution of radioactivity was determined via PET at 60 min after radiotracer injection. PET and CT images were acquired 10 d after tumor inoculation, to establish baseline distribution and uptake, and then on selected days after surgical tumor resection. CT images and caliper were used to determine the tumor volume. Radiotracer uptake was assessed by (18)F-AH113804 PET imaging. c-Met expression was assessed by immunofluorescence imaging of tumor samples and correlated with (18)F-AH113804 PET imaging results.
Baseline uptake of (18)F-AH113804, determined in tumor-bearing animals after 10 d, was approximately 2-fold higher in the tumor than in muscle tissue or the contralateral mammary fat pad. The tumor growth rate, determined from CT images, was comparable between the animals with recurrent tumors, with detection of tumors of low volume (<10 mm(3)) only possible by day 20 after tumor resection. (18)F-AH113804 PET detected local tumor recurrence as early as 6 d after surgery in the recurrent tumor-bearing animals and exhibited significantly higher (18)F-AH113804 uptake (in comparison to mammary fatty tissue), with a target-to-background (muscle) ratio of approximately 3:1 (P < 0.01). The c-Met expression of individual resected tumor samples, determined by immunofluorescence, correlated with the respective (18)F-AH113804 imaging signals (r = 0.82, P < 0.05).
(18)F-AH113804 PET provides a new diagnostic tool for the detection of c-Met-expressing primary tumor and has potential utility for the detection of locoregional recurrence from an early stage.
乳腺癌的局部区域复发会引发严重的临床问题，因为一旦胸壁受累，通常就无法进行手术。利用针对可治疗的靶向受体（如c-Met）的分子成像剂早期检测复发可能会带来潜在益处。本研究的目的是评估（18）F-AH113804，一种对人c-Met具有高亲和力的基于肽的分子成像剂，用于在人基底样乳腺癌模型HCC1954中检测早期局部区域复发。
建立携带HCC1954肿瘤的异种移植模型，并给予（18）F-AH113804。在注射放射性示踪剂后60分钟通过PET确定放射性分布。在接种肿瘤后10天采集PET和CT图像，以建立基线分布和摄取情况，然后在手术切除肿瘤后的选定日期采集。使用CT图像和卡尺确定肿瘤体积。通过（18）F-AH113804 PET成像评估放射性示踪剂摄取。通过肿瘤样本的免疫荧光成像评估c-Met表达，并将其与（18）F-AH113804 PET成像结果相关联。
在携带肿瘤的动物中，10天后确定的（18）F-AH113804的基线摄取在肿瘤中的水平比肌肉组织或对侧乳腺脂肪垫中高约2倍。根据CT图像确定的肿瘤生长速率在复发性肿瘤的动物之间相当，仅在肿瘤切除后第20天才能检测到小体积（<10 mm（3））的肿瘤。（18）F-AH113804 PET在携带复发性肿瘤的动物中最早在手术后6天检测到局部肿瘤复发，并且显示出明显更高的（18）F-AH113804摄取（与乳腺脂肪组织相比），靶本比（肌肉）约为3:1（P < 0.01）。通过免疫荧光确定的各个切除肿瘤样本的c-Met表达与相应的（18）F-AH113804成像信号相关（r = 0.82, P < 0.05）。
（18）F-AH113804 PET为检测表达c-Met的原发性肿瘤提供了一种新的诊断工具，并且在早期检测局部区域复发方面具有潜在用途。
