Preclinical characterization of 18F-D-FPHCys, a new amino acid-based PET tracer
| العنوان: | Preclinical characterization of 18F-D-FPHCys, a new amino acid-based PET tracer |
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| المؤلفون: | Rodney J. Hicks, Laura Kirby, Peter Roselt, Oliver C. Neels, Delphine Denoyer, Rachael Shepherd, Andrew Katsifis, Kelly Waldeck, Thomas Bourdier |
| المصدر: | European Journal of Nuclear Medicine and Molecular Imaging. 39:703-712 |
| بيانات النشر: | Springer Science and Business Media LLC, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Biodistribution, Large Neutral Amino Acid-Transporter 1, Mice, chemistry.chemical_compound, Cell Line, Tumor, Animals, Humans, Radiology, Nuclear Medicine and imaging, Amino acid transporter, Radioactive Tracers, Tyrosine, Homocysteine, Cell Proliferation, chemistry.chemical_classification, Methionine, System L, Chemistry, business.industry, Biological Transport, General Medicine, In vitro, Amino acid, Cell Transformation, Neoplastic, Gene Expression Regulation, Biochemistry, Positron-Emission Tomography, Nuclear medicine, business |
| الوصف: | The imaging potential of a new (18)F-labelled methionine derivative, S-(3-[(18)F]fluoropropyl)-D-homocysteine ((18)F-D-FPHCys), and its selectivity for amino acid transporter subtypes were investigated in vitro and by imaging of human tumour xenografts.Expression of members of the system L (LAT isoforms 1-4 and 4F2hc) and ASCT (ASCT isoforms 1 and 2) amino acid transporter subclasses were assessed by quantitative real-time PCR in four human tumour models, including A431 squamous cell carcinoma, PC3 prostate cancer, and Colo 205 and HT-29 colorectal cancer lines. The first investigations for the characterization of (18)F-D-FPHCys were in vitro uptake studies by comparing it with [1-(14)C]-L-methionine ((14)C-MET) and in vivo by PET imaging. In addition, the specific involvement of LAT1 transporters in (18)F-D-FPHCys accumulation was tested by silencing LAT1 mRNA transcription with siRNAs. To determine the proliferative activity in tumour xenografts ex vivo, Ki-67 staining was used as a biomarker.A431 cells showed the highest (18)F-D-FPHCys uptake in vitro and in vivo followed by Colo 205, PC3 and HT-29. A similar pattern of retention was observed with (14)C-MET. (18)F-D-FPHCys retention was strongly correlated with LAT1 expression both in vitro (R(2) = 0.85) and in vivo (R(2) = 0.99). Downregulation of LAT1 by siRNA inhibited (18)F-D-FPHCys uptake, demonstrating a clear dependence on this transporter for tumour uptake. Furthermore, (18)F-D-FPHCys accumulation mirrored cellular proliferation.The favourable properties of (18)F-D-FPHCys make this tracer a promising imaging probe for detection of tumours as well as for the noninvasive evaluation and monitoring of tumour growth. |
| تدمد: | 1619-7089 1619-7070 |
| DOI: | 10.1007/s00259-011-2017-4 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8ef674d02261dd8c4073d635f3bd87f5 https://doi.org/10.1007/s00259-011-2017-4 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....8ef674d02261dd8c4073d635f3bd87f5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16197089 16197070 |
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| DOI: | 10.1007/s00259-011-2017-4 |