Abstract
Loco-regional recurrence of breast cancer poses significant clinical problems due to 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 loco-regional 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 positron emission tomography (PET) at 60 min post radiotracer injection. PET and CT (computerized tomography) images were acquired 10 days 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 days, was approximately 2-fold higher in the tumor as compared to 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 post tumor resection. [18F]AH113804 PET detected local tumor recurrence as early as six days 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 loco-regional recurrence from an early stage.
- Animal Imaging
- Oncology: Breast
- PET/CT
- AH113804
- PET/CT imaging
- basal-like breast cancer
- c-Met
- loco-regional recurrence
- Copyright © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.