c-Met PET Imaging Detects Early-Stage Locoregional Recurrence of Basal-Like Breast Cancer

Appitha Arulappu, Mark Battle, Michel Eisenblaetter, Graeme McRobbie, Imtiaz Khan, James Monypenny, Gregory Weitsman, Myria Galazi, Susan Hoppmann, Patrycja Gazinska, Wulan Wulaningsih, Grethe Tang Dalsgaard, Sven Macholl, Tony Ng

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24 Citations (Scopus)
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Abstract

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 18F-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. Methods: HCC1954 tumor–bearing xenograft models were established, and 18F-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 18F-AH113804 PET imaging. c-Met expression was assessed by immunofluorescence imaging of tumor samples and correlated with 18F-AH113804 PET imaging results. Results: Baseline uptake of 18F-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 mm3) only possible by day 20 after tumor resection. 18F-AH113804 PET detected local tumor recurrence as early as 6 d after surgery in the recurrent tumor–bearing animals and exhibited significantly higher 18F-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 18F-AH113804 imaging signals (r = 0.82, P < 0.05). Conclusion: 18F-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.                   

Original languageEnglish
Pages (from-to)765-70
Number of pages6
JournalJournal of Nuclear Medicine
Volume57
Issue number5
Early online date3 Dec 2015
DOIs
Publication statusPublished - 1 May 2016

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