Appitha Arulappu1, Mark Battle2, Michel Eisenblaetter3, Graeme McRobbie2, Imtiaz Khan2, James Monypenny1, Gregory Weitsman1, Myria Galazi1, Susan Hoppmann2, Patrycja Gazinska4, Wulan Wulaningsih1, Grethe Tang Dalsgaard2, Sven Macholl5, Tony Ng6. 1. Richard Dimbleby Department of Cancer Research, Kings College London, London, United Kingdom. 2. GE Healthcare, Life Sciences, Amersham, United Kingdom. 3. Richard Dimbleby Department of Cancer Research, Kings College London, London, United Kingdom Division of Imaging Sciences & Biomedical Engineering, King's College London, London, United Kingdom Department of Clinical Radiology, University Hospital Münster, Münster, Germany. 4. Breast Cancer NOW Unit, King's College London School of Medicine, London, United Kingdom. 5. GE Healthcare, Life Sciences, Amersham, United Kingdom Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; and. 6. Richard Dimbleby Department of Cancer Research, Kings College London, London, United Kingdom Breast Cancer NOW Unit, King's College London School of Medicine, London, United Kingdom UCL Cancer Institute, University College London, London, United Kingdom tony.ng@kcl.ac.uk.
Abstract
UNLABELLED: 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. METHODS: 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. 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). CONCLUSION: (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.
UNLABELLED: 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. METHODS: 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. 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). CONCLUSION: (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.
Authors: Martin Pool; Anton G T Terwisscha van Scheltinga; Arjan Kol; Danique Giesen; Elisabeth G E de Vries; Marjolijn N Lub-de Hooge Journal: Eur J Nucl Med Mol Imaging Date: 2017-03-19 Impact factor: 9.236
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